Film-coated tablets that should be swallowed whole and can be taken with or without food.
A high-fat meal increased combined AUC of Abemaciclib and its active metabolites by 9 % and increased Cmax
by 26 %.
Abemaciclib exhibits pH dependent solubility and is considered highly soluble up to pH 6.0, solubility is
decreased then.
Absorption site unknown.
Lipophilic molecule → clog P = 5.5
BCS Class 3
Lipophilic molecule and pH dependent solubility → risk of decreased absorption
Chen P, Lee NV, Hu W, Xu M, Ferre RA, Lam H, et al. Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance. Mol Cancer Ther. oct 2016;15(10):2273‑81.
The tablets must be swallowed whole and taken on an empty stomach (at least one hour before or two hours after eating)
Administration of Abiraterone acetate with food → up to a 10-fold (AUC) and up to a 17-fold (Cmax) increase in mean systemic exposure. Abiraterone has no pH dependent solubility in aqueous media in a pH range of 1.2 to 9.8 - Practically insoluble in water – weakly basic compound Small intestine absorption
Highly lipophilic molecule → Log P = 5.12 BCS class 4
Drug interaction with antioxidant: Vitamin C and E (high dose)
Highly lipophilic molecule and has low solubility and permeability → risk of altered absorption
Geboers S, Stappaerts J, Mols R, Snoeys J, Tack J, Annaert P, et al. The Effect of Food on the Intraluminal Behavior of Abiraterone Acetate in Man. J Pharm Sci. sept 2016;105(9):2974-81. Beg S, Malik AK, Ansari MJ, Malik AA, Ali AMA, Theyab A, et al. Systematic Development of Solid Lipid Nanoparticles of Abiraterone Acetate with Improved Oral Bioavailability and Anticancer Activity for Prostate Carcinoma Treatment. ACS Omega. 24 mai 2022;7(20):16968-79.
The capsules should be swallowed whole with water with or without food. The capsules should not be chewed, dissolved or opened.
Taken with a high-fat meal → no modification of the mean AUC, Cmax decreased by 69% and Tmax delayed for 1-2 hours Acalabrutinib exhibits pH-dependent solubility in aqueous media → solubility of acalabrutinib decreases with increasing pH → highly soluble in aqueous media at pH 4 and below but with low solubility above pH 4 Intestinal absorption
Weakly lipophilic molecule → Log P = 0.49 Weak base, BCS class 2 compound with BCS class 1 like behaviour in vivo under normal stomach pH conditions
Drug interaction: vitamin E supplementation may increase the risk of bleeding
Low solubility above pH 4 → risk of altered absorption Vitamine E supplementation → monitor the increased risk of bleeding Proton pump inhibitors → Avoid concomitant use H2-receptor antagonists → Take Acalabrutinib 2 hours before (or 10 hours after) taking a H2-receptor antagonist. Antacids → The interval between taking the medicinal products should be at least 2 hours.
Mudie DM, Stewart AM, Rosales JA, Biswas N, Adam MS, Smith A, et al. Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs. Pharmaceutics. 15 avr 2021;13(4):557.
Film-coated tablets that must be swallowed whole and taken on an empty stomach (at least one hour before or three hours after eating). The tablets can be dispersed in approximately 100 mL of non-carbonated drinking water.
Administration with a high-fat meal → decrease of exposure to afatinib by about 50% in regard to Cmax and 39% in regard to AUC Highly soluble molecule throughout the physiological pH range of 1–7.5. Intestinal absorption
Afatinib is a basic compound with high lipophilicity Log P = 4,7 (pH > 9) No conclusive placement of afatinib in the Biopharmaceutics Classification System but it should be considered as either a BCS class 1 or 3
Highly lipophilic drug → risk of altered absorption
Schnell D, Buschke S, Fuchs H, Gansser D, Goeldner RG, Uttenreuther-Fischer M, et al. Pharmacokinetics of afatinib in subjects with mild or moderate hepatic impairment. Cancer Chemother Pharmacol. août 2014;74(2):267-75. Zhang Y, Wang C, Liu Z, Meng Q, Huo X, Liu Q, et al. P-gp is involved in the intestinal absorption and biliary excretion of afatinib in vitro and in rats. Pharmacol Rep. avr 2018;70(2):243-50. Wind S, Schnell D, Ebner T, Freiwald M, Stopfer P. Clinical Pharmacokinetics and Pharmacodynamics of Afatinib. Clin Pharmacokinet. mars 2017;56(3):235-50.
Hard capsules should be swallowed whole and taken with food (administration by gastric tube possible CNHIM).
Administration with a high-fat meal → Alectinib and its metabolite exposure was increased by around 3-fold relative to fasted conditions. Alectinib has low solubility in aqueous buffers across the pH range → solubility decreases with increasing pH in vitro Absorption site unknown
Weak base and lipophilic molecule → log P = 1.96 BCS class 4
Low solubility and lipophilic drug → risk of decreased absorption → Capsules can be opened to avoid the dissolution No dose adjustments are required when Alectinib is co-administered with proton pump inhibitors or other medicinal products which raise gastric pH.
Zhao D, Chen J, Chu M, Long X, Wang J. Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review. Drug Des Devel Ther. 30 avr 2020;14:1663-81.
Film-coated tablets that should be swallowed whole and taken immediately after food. Gastrointestinal solubility is increased by bile, secreted in response to food intake.
It exhibits pH-dependent solubility → practically insoluble in aqueous media above pH 2 and slightly soluble in pH 1. Absorption site unknown
Weak base and lipophilic molecule: log P = 2.95 BCS class 2
Practically insoluble in aqueous media above pH 2 and lipophilic drug → risk of decreased absorption The solubility of Alpelisib is dependent on biliary secretions which are modified by RYGB → risk of altered absorption Alpelisib can be co-administered with acid-reducing agents, provided Alpelisib is taken immediately after food.
El-Khouly OA, Henen MA, El-Sayed MAA, Shabaan MI, El-Messery SM. Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study. Bioorg Med Chem. 1 févr 2021;31:115976.
Capsules should be swallowed whole and taken after a meal and before bedtime.
Altretamine is practically insoluble in water but is increasingly soluble at pH 3 and below Its absorption is limited by its poor solubility Absorption site unknown
BCS class 2
Drug interaction with antioxidant: Vitamin C and E (high dose)
Risk of decreased efficiency of Altretamine due to Vitamin C and E supplementation (Altretamine is a prodrug that requires activation by hepatic oxidative metabolism)
Gidwani B, Vyas A. Preparation, characterization, and optimization of altretamine-loaded solid lipid nanoparticles using Box-Behnken design and response surface methodology. Artif Cells Nanomed Biotechnol. 2016;44(2):571-80.
Capsules that should be swallowed whole and taken with or without food
Anagrelide exhibits pH-dependent solubility → only slightly soluble between pH 3-10. Absorption site unknown
Lipophilic molecule log P = 2.4 BCS class 4
Drug interaction: vitamin E supplementation may increase the risk of bleeding
Lipophilic molecule and pH-dependent solubility → risk of decreased absorption Monitor the increased risk of bleeding
Film-coated tablets that can be taken with or without food. The tablets can be crushed
Moderate aqueous solubility → solubility is PH-independent in the physiological range Absorption site unknown
Moderately lipophilic compound → log P = 1.58 BCS class 2
Moderately lipophilic compound → low risk of altered absorption
Piotrowska I, Piotrowska M. Anastrozole as aromatase inhibitor – new approaches to breast cancer treatment in postmenopausal women. Nowotwory Journal of Oncology. 2019;69(1):26‑35. Consequence of ANASTROZOLE on Chemo therapy | https://www.auctoresonline.org/article/consequence-of-anastrozole-on-chemo-therapy
Film-coated tablets that should be swallowed whole and can be taken with or without food.
Co administration with a high-fat meal → no clinically relevant changes in Cmax and AUC, Tmax was delayed about 2 hours with food. Not ionizable under relevant physiological pH condition → acid lowering agents (proton pump inhibitor, H2-receptor antagonist, antacid) are not expected to affect the solubility and bioavailability of apalutamide. Predicted to have high permeability in the human intestine
Practically insoluble in aqueous media over a wide range of pH values (1-12). Log P = 3.90 BCS class 2
Lipophilic molecule → risk of altered absorption
Vries R de, Jacobs F, Mannens G, Snoeys J, Cuyckens F, Chien C, et al. Apalutamide Absorption, Metabolism, and Excretion in Healthy Men, and Enzyme Reaction in Human Hepatocytes. Drug Metab Dispos. 1 mai 2019;47(5):453-64. Volkova TV, Drozd KV, Surov AO. Effect of polymers and cyclodextrins on solubility, permeability and distribution of enzalutamide and apalutamide antiandrogens. Journal of Molecular Liquids. 15 janv 2021;322:114937.
Film-coated tablets that should be swallowed whole. Food must be avoided for at least 2 hours before and 1 hour after taking Asciminib
The AUC and Cmax of asciminib decreased by 62% and 68%, respectively, with a high-fat meal compared to the fasted state. pH-dependent solubility. Absorption site unknown.
FDA agrees that asciminib hydrochloride is a low solubility drug substance, and can be classified as either a BCS class 2 or 4
pH-dependent solubility → risk of altered absorption
Tran P, Hanna I, Eggimann FK, Schoepfer J, Ray T, Zhu B, et al. Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects. Xenobiotica. févr 2020;50(2):150-69.
Film-coated tablets that must be swallowed whole and taken on an empty stomach at least 1 hour before or at least 2 hours after a meal.
After a high fat meal → Cmax and AUCinf were increased by 59% and 29% pH-dependent solubility ,decreases with increasing pH Absorption site unknown.
Lipophilic molecule LogP = 3.20 May be classified as a low soluble and moderate permeability BCS Class 2 or 4 drug substance
pH-dependent solubility and lipophilic molecule → risk of decreased absorption
Film-coated tablets that should be swallowed whole with or without food.
A high fat, high-calorie meal resulted in 19% higher exposure compared to overnight fasting. pH-dependent solubility with higher pH resulting in lower solubility Absorption site unknown
Weak base BCS class 2
Drug interaction : vitamin E supplementation may increase the risk of bleeding Drug-drug interaction studies indicate a 15% decrease in axitinib AUC and 42% decrease in axitinib Cmax when administered with rabeprazole.
pH-dependent solubility → risk of altered absorption
Film-coated tablets that should be swallowed whole with or without food
The impact of food on the exposure is minimal. Absorption site unknown
Highly soluble in aqueous media across physiologic pH (pH 1-7. 7) range. FDA has not designated the BCS class for this product
Not enough information available to conclude on absorption after RYGB
Soft capsules that must be taken with a meal and swallowed intact and not chewed.
AUC and Cmax values increased following the administration of a fat-containing meal versus those following the administration of a glucose solution PH-dependent aqueous solubility predicted - predicted to be slightly higher in basic pH conditions Absorption site unknown
Highly lipophilic drug - Log P = 6.9 BCS class 2
Slightly higher solubilty in basic pH conditions but highly lipophilic drug → risk of altered absorption
Li L, Liu Y, Wang J, Chen L, Zhang W, Yan X. Preparation, in vitro and in vivo evaluation of bexarotene nanocrystals with surface modification by folate-chitosan conjugates. Drug Deliv. 2016;23(1):79-87.
Lee JB, Kim TH, Feng W, Choi HG, Zgair A, Shin S, et al. Quantitative Prediction of Oral Bioavailability of a Lipophilic Antineoplastic Drug Bexarotene Administered in Lipidic Formulation Using a Combined In Vitro Lipolysis/Microsomal Metabolism Approach. Journal of Pharmaceutical Sciences. 1 févr 2019;108(2):1047-52.
Film-coated tablets that can be crushed and taken with or without food
pH-independent solubility
Lipophilic drug : Log P =2.92 BCS class 2
Lipophilic drug → risk of altered absorption
Mi̇ttal A, Shri̇vastava A. Separation of Four Impurities and Degradants by LC: A Case of Bicalutamide. Hacettepe University Journal of the Faculty of Pharmacy. 1 juin 2021;41(2):82-92.
Volkova TV, Simonova OR, Perlovich GL. Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability. Pharmaceutics. 18 mars 2022;14(3):674.
Film-coated tablets that must be swallowed whole with water. Tablets may be taken with or without food
Administration of a single 45 mg dose of binimetinib with a high-fat, high-calorie meal decreased Cmax by 17 %, AUC was unchanged. pH-dependent solubility : low solubility at physiological pH but higher at acidic pH Absorption site unknown
Lipophilic drug Log P = 3.81 BCS class 4
A drug interaction study in healthy subjects indicated that the extent of binimetinib exposure is not altered in the presence of a gastric pH-altering agent
pH-dependent solubility and lipophilic drug → risk of decreased absorption , the extent of binimetinib exposure is not altered in the presence of a gastric pH-altering agent
Film-coated tablets can be crushed, dissolved or dispersed in a glass of water and should be taken orally once daily with food
Food increased bosutinib Cmax 1.8-fold and bosutinib AUC 1.7-fold compared to the fasting state pH-dependent solubility , absorption is reduced when gastric pH is increased Absorption site unknown
Lipophilic drug : Log P = 4.1 BCS class 4
Drug interaction with antioxidant: Vitamin C and E (high dose)
pH-dependent solubility, solubility reduces rapidly above pH 5, lipophilic molecule → risk of decreased absorption → tablets can be crushed, dissolved or dispersed in a glass of water.
Schmitt MV, Reichel A, Liu X, Fricker G, Lienau P. Extension of the Mechanistic Tissue Distribution Model of Rodgers and Rowland by Systematic Incorporation of Lysosomal Trapping: Impact on Unbound Partition Coefficient and Volume of Distribution Predictions in the Rat. Drug Metab Dispos. janv 2021;49(1):53-61.
Film-coated tablets that should be swallowed whole and with water and can be administered with or without food.
Compared to overnight fasting, a high fat meal reduced brigatinib Cmax by 13% with no effect on AUC. pH dependent solubility : solubility decreasing as pH values increase from 1.6 to 7.5 Absorption site unknown
Highly lipophilic drug : LogP = 5.17 Considered BCS 1
Solubility decreasing as pH values increase and highly lipophilic molecule → high risk of decreased absorption
Zhao D, Chen J, Chu M, Long X, Wang J. Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review. Drug Des Devel Ther. 30 avr 2020;14:1663-81.
Film-coated tablets that must be swallowed whole and can be administered with or without food
Oral bioavailability of busulfan is subject to strong intra-individual variability - Busulfan clearance has been shown to be increased in obesity Absorption site unknown
Log P = -0.58
Few absorption modification due to RYGB - Administration based on body surface area or adjusted to ideal body weight should be considered in obese patients
Główka FK, Romański M, Siemiątkowska A. Determination of partition coefficients n-octanol/water for treosulfan and its epoxy-transformers: An example of a negative correlation between lipophilicity of unionized compounds and their retention in reversed-phase chromatography. Journal of Chromatography B. 1 avr 2013;923-924:92-7.
Film-coated tablets that should be swallowed whole and should be taken 1 hour before or 2 hours after eating.
A high-fat meal moderately increased Cmax and AUC values (41% and 57%, respectively) compared to fasted conditions. pH-dependent solubility → very low solubility observed at pH >3. Absorption site unknown
BCS class 2
Co-administration of esomeprazole with a single dose of 100 mg cabozantinib resulted in no clinically-significant effect on plasma cabozantinib exposure (AUC).
pH-dependent solubility, with very low solubility observed at a pH >3 → risk of altered absorption No dose adjustment is indicated when gastric pH modifying agents (PPIs, H2 receptor antagonists, and antacids) are co-administered with cabozantinib.
Film-coated tablets that should not be crushed or cut and should be taken within 30 minutes after a meal
Administration with food decreases the rate of capecitabine absorption, but only results in a minor effect on the AUC of capecitabine's metabolites. Absorption site unknown
Log P = 0.4 Available data on solubility does not allow the BCS classification of capecitabine
Current data suggest that availability of gastric fluid is not required for the dissolution of capecitabine. The passage rate of capecitabine into the small bowel is increased after (partial) gastrectomy, which resulted in quick intestinal availability of capecitabine. Furthermore, this also implies adequate bioavailability of capecitabine and metabolites in cancer patients who have a history of bariatric surgery (i.e., Roux-en-Y gastric bypass) Interaction : Folinate supplementation may increase capecitabine's toxicity
Weakly lipophilic molecule → low risk of altered absorption
Jacobs BAW, Deenen MJ, Joerger M, Rosing H, de Vries N, Meulendijks D, et al. Pharmacokinetics of Capecitabine and Four Metabolites in a Heterogeneous Population of Cancer Patients: A Comprehensive Analysis. CPT Pharmacometrics Syst Pharmacol. déc 2019;8(12):940-50.
Lunar N, Etienne-Grimaldi MC, Macaire P, Thomas F, Dalenc F, Ferrero JM, et al. Population pharmacokinetic and pharmacodynamic modeling of capecitabine and its metabolites in breast cancer patients. Cancer Chemother Pharmacol. févr 2021;87(2):229-39.
Film-coated tablets that should be swallowed whole and administered with or without food
A high-fat meal in healthy subjects increased capmatinib AUC0-INF by 46% with no change in Cmax compared to under fasted conditions Absorption site unknown
pH-dependent solubility BCS class 2
pH-dependent solubility → risk of altered absorption
Hard capsules that should be swallowed whole with water, should not be chewed or crushed and should be taken with food.
Systemic exposure of ceritinib was increased when administered with food. Ceritinib AUCinf value were 73% higher and Cmax 41% higher when administration with a high fat meal compared to the fasted state. Solubility decreases as pH values increase from 1 to 6.8 Absorption site unknown
Weakly-basic agent with high lipophilicity Log P = 4.6 BCS class 4
Coadministration of PPIs possibly reduces absorption of ceritinib Drug interaction with antioxidant: Vitamin C and E (high dose)
pH-dependent solubility and lipophilic drug → risk of decreased absorption , caution when ceritinib is administered with PPIs → risk of decreased exposure
Zhao D, Chen J, Chu M, Long X, Wang J. Pharmacokinetic-Based Drug–Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review. Drug Des Devel Ther. 30 avr 2020;14:1663-81.
Hard capsules that should be swallowed whole and taken on an empty stomach
Chlorambucil is well absorbed by passive diffusion in the gastrointestinal tract Intestinal absorption
Log P = 1.70
Lipophilic molecule → risk of altered absorption
Adair CG, McElnay JC. Studies on the mechanism of gastrointestinal absorption of melphalan and chlorambucil. Cancer Chemother Pharmacol. 1986;17(1):95-8.
Film-coated tablets that should be swallowed whole with water with or without food.
The pharmacokinetics of cobimetinib are not altered when administered in the fed state (high-fat meal) compared with the fasted state in healthy subjects pH-dependent solubility Absorption site unknown
BCS class 1
HpH-dependent solubility → risk of altered absorption
van Berge Henegouwen JM, van der Wijngaart H, Zeverijn LJ, Hoes LR, Meertens M, Huitema ADR, et al. Efficacy and toxicity of vemurafenib and cobimetinib in relation to plasma concentrations, after administration via feeding tube in patients with BRAF-mutated thyroid cancer: a case series and review of literature. Cancer Chemother Pharmacol. juill 2022;90(1):97-104.
Hard capsules that should be swallowed whole (but can be administered via a feeding tube by performing a dissolution of the capsule in lukewarm water) and taken with or without food
A high-fat meal reduced crizotinib AUCinf and Cmax by approximately 14% (250mg dose) pH-dependent solubility → a higher pH result in lower solubility. Absorption site unknown
Log P = 1.83 Designed as BCS class 4 drug. However, it has not received official BCS
pH-dependent solubility and lipophilic drug → risk of decreased absorption
Knapen L, Dingemans A-M, Croes S. Administration of crizotinib via jejunostomy tube: A case report. OA Journal of Clinical Case Reports. 2018;1:005. doi: 10.33118/oaj.clin.2019.01.005 Koji Tamai, Kazuma Nagata, Kyoko Otsuka, Atsushi Nakagawa, Ryo Tachikawa, Kojiro Otsuka, Nobuyuki Katakami, Keisuke Tomii. Crizotinib administered via nasogastric and percutaneous endoscopic gastrostomy tubes for the successful treatment of ALK-rearranged lung cancer in a patient with poor performance status, Respiratory Investigation, Volume 51, Issue 1,2013,Pages 46-48,ISSN 2212-5345, https://doi.org/10.1016/j.resinv.2012.12.001.
Film-coated tablets that should be swallowed whole administered in the morning on an empty stomach, combining sufficient absorption of drink at the time of taking and immediately after.
No relevant information Absorption site unknown
Log P = 0.8 predicted BCS class 1
Cyclophosphamide for injection can be orally administered
Weakly lipophilic molecule → few risk of altered absorption
Custodio JM, Wu CY, Benet LZ. Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption. Adv Drug Deliv Rev. 17 mars 2008;60(6):717‑33. Kennedy R, Groepper D, Tagen M, Christensen R, Navid F, Gajjar A, et al. Stability of cyclophosphamide in extemporaneous oral suspensions. Ann Pharmacother. févr 2010;44(2):295‑301.
Hard capsules that must be swallowed whole at least one hour before, or at least 2 hours after a meal.
Administration with food reduced the bioavailability (Cmax and AUC decreased by 51% and 31% respectively) and delayed the absorption when compared to the fasted state. pH-dependent with decreased solubility at higher pH Absorption site unknown
Lipophilic molecule : LogP = 2.9 BCS class 2
Medicinal products that alter the pH of the upper gastrointestinal (GI) tract (e.g. proton pump inhibitors, H2-receptor antagonists, antacids) are not expected to reduce the bioavailability of dabrafenib Case report : 62 years old woman treated with Dabrafenib 150mg twice a day and Trametinib 2mg daily for a metastatic BRAF V600E mutated melanoma with a complete response. Underwent sleeve gastrectomy for morbid obesity → successfull procedure and still complete response for the patient suggesting that this procedure did not impair the efficacy of Dabrafenib and Trametinib
pH-dependent solubility and lipophilic drug → risk of decreased absorption, oral solution (AAC) can be used
Velter C, Sakkal M, Robert C. Bariatric surgery in a patient treated with targeted therapies for metastatic melanoma: a case report. Melanoma Res. déc 2020;30(6):629‑30.
Film-coated tablets that should be swallowed whole with or without a meal
Food does not alter bioavailability to a clinically meaningful extent. pH-dependent solubility → acidic pH result in higher solubility Absorption site unknown
Lipophilic molecule : Log P = 3.92 BCS class 2
PPIs should be avoided while receiving treatment with dacomitinib
pH-dependent solubility and lipophilic drug → risk of decreased absorption
Film-coated tablets that should be swallowed whole and can be taken with or without food.
Co administration with a high-fat meal → 14% increase in the mean AUC of dasatinib
Absorption site unknown
Exhibits pH dependent aqueous solubility - Dasatinib solubility decreases at pH>4
BCS class 2
Undesirable effects: Neuropathy → B1/B6 Vitamins supplementation is recommended
Morbidly obese woman treated with Dasatinib 100 mg once daily and achieved a complete molecular response underwent sleeve gastrectomy and lost her hematological response
Solubility decreases at pH > 4 → risk of altered absorption If decreased absorption → Possible off-label use of oral suspension Antacids may be administered up to 2 hours prior to or 2 hours following Dasatinib
Levêque D, Becker G, Bilger K, Natarajan-Amé S. Clinical Pharmacokinetics and Pharmacodynamics of Dasatinib. Clin Pharmacokinet. juill 2020;59(7):849-56.
Hard capsules that should be swallowed whole with or without food.
Administration with a high-fat meal decreased Cmax by approximately 37% and decreased the AUC by approximately 6%, relative to fasting conditions. pH-dependent solubility with low solubility at pH>3 Intestinal absorption
Highly lipophilic compound Log P = 4.55 BCS class 4
pH-dependent solubility and highly lipophilic drug → high risk of decreased absorption
Sayed AY, Khalil NY, Almomen A, Alzoman NZ, Almehizia AA, Darwish IA. A Highly Sensitive Nonextraction-Assisted HPLC Method with Fluorescence Detection for Quantification of Duvelisib in Plasma Samples and its Application to Pharmacokinetic Study in Rats. Drug Des Devel Ther. 21 juin 2021;15:2667‑77.
Film-coated tablets that should be swallowed whole with or without food.
No relevant information Absorption site unknown
BCS class 2
Not enough information available to conclude on absorption after RYGB
Hard capsules that should be swallowed whole with or without food
Free base and its solubility is strongly pH-dependent: it exhibits higher solubility at lower pH relative to higher pH. Intestinal absorption
Very high lipophilicity/amphiphilicity BCS class 4
Entrectinib specific adverse event: fractures → Calcium and vitamin D supplementation
Strongly pH-dependent solubility and highly lipophilic drug → high risk of decreased absorption Calcium and vitamin D supplementation recommended especially for RYGB population (vitamin malabsorption). No dose adjustments are required when entrectinib is co-administered with PPIs or other drugs that raise gastric pH (e.g., H2 receptor antagonists or antacids).
Entrectinib, a TRK/ROS1 inhibitor with anti-CNS tumor activity: differentiation from other inhibitors in its class due to weak interaction with P-glycoprotein | Neuro-Oncology | Oxford Academic : https://academic.oup.com/neuro-oncology/article/22/6/819/5834590
Tablets that should be swallowed whole and can be taken with or without food.
High fat meals → reduced AUC by 22% and the peak plasma concentration Cmax by 54%. Light fat meals → reduced AUC by 32% and Cmax by 42% Intestinal absorption
Practically insoluble in water Lipophilic drug
53 years old woman who underwent liver transplant and sleeve gastrectomy - The patient received standard immunosuppression consisting of tacrolimus once daily and everolimus → Autors managed to maintain adequate immunosuppression levels, without the difficulties encountered in malabsorptive procedures (immunosuppressive indication)
Lipophilic molecule → risk of altered absorption - Possible off-label use of Votubia® dispersible tablets.
Tariciotti L, D’Ugo S, Manzia TM, Tognoni V, Sica G, Gentileschi P, et al. Combined liver transplantation and sleeve gastrectomy for end-stage liver disease in a bariatric patient: First European case-report. Int J Surg Case Rep. 2016;28:38-41.
Hard capsules that should be swallowed whole with or without food
A highfat, high-calorie meal decreased the Cmax by 36%, while the AUC was unchanged pH-dependent solubility Absorption site unknown
BCS class 2
Drug interaction : vitamin E supplementation may increase the risk of bleeding
pH-dependent solubility → risk of altered absorption - Vitamine E supplementation → monitor the increased risk of bleeding
Soft capsules that should be swallowed whole with or without food
Food has no clinically significant effect on the extent of absorption elevant pH enzalutamide solubility is not affected by pH over the physiological range Absorption site unknown
cLog P = 2.98
lipophilic drug → risk of altered absorption
Film-coated tablets that should be swallowed whole with or without food
Administration with a high-fat, high-calorie meal did not affect erdafitinib pharmacokinetics Absorption site unknown
BCS class 1
Drug interaction : avoid association with: Chelating agents: lanthanum carbonate, calcium acetate, sevelamer, Vitamin D, potassium, phosphate, calcium because erdafitinib causes hyperphosphatemia
Not enough information available to conclude on absorption after RYGB Calcium and vitamin D supplementation → monitor the risk of hyperphosphatemia due to erdaftinib
Film-coated tablets that should be taken at least one hour before or two hours after the ingestion of food and should be swallowed whole.
The exposure after an oral dose may be increased by food. pH-dependent solubility → Solubility decreases as pH increases. Intestinal absorption
Weak base – Lipophilic compound : Log P =2.7 BCS class 2
Drug interaction with antioxidant: Vitamin C and E (high dose)
pH-dependent solubility and lipophilic drug → risk of decreased absorption The combination of erlotinib with proton pump inhibitors should be avoided. If the use of antacids is considered necessary during treatment with erlotinib, they should be taken at least 4 hours before or 2 hours after the daily dose of erlotinib. If the use of ranitidine is considered, it should be used in a staggered manner; must be taken at least 2 hours before or 10 hours after ranitidine dosing
Gruber A, Czejka M, Buchner P, Kitzmueller M, Kirchbaumer Baroian N, Dittrich C, et al. Monitoring of erlotinib in pancreatic cancer patients during long-time administration and comparison to a physiologically based pharmacokinetic model. Cancer Chemother Pharmacol. 2018;81(4):763‑71.
Jahangiri A, Khalilzad F, Barghi L. Dissolution improvement of binary solid dispersions of erlotinib prepared by one-step electrospray method. Biol Methods Protoc. 2022;7(1):bpac001.
Pérez-Pitarch A, Guglieri-López B, Nacher A, Merino V, Merino-Sanjuan M. Levofloxacin effect on erlotinib absorption. Evaluation of the interaction in undernutrition situations through population pharmacokinetic analysis in rats. Biopharm Drug Dispos. juill 2017;38(5):315‑25.
Hard capsules that should be taken at least one hour before or two hours after the ingestion of food and should be swallowed whole.
Milk, milk products, and calcium-rich foods or drugs may impair the absorption. Absorption site unknown
Predicted lipophilic molecule: predicted log P = 3.92
Drug interaction: calcium or magnesium supplementation, milk, other dairy products
lipophilic drug → risk of altered absorption (based on predicted log P) - Not enough information available to conclude on absorption after RYGB- estramustine must be taken 2 hours before or after calcium or magnesium salts.
Omachi F, Kaneko M, Iijima R, Watanabe M, Itagaki F. Relationship between the effects of food on the pharmacokinetics of oral antineoplastic drugs and their physicochemical properties. J Pharm Health Care Sci. 2019;5:26.
Soft capsules that should be taken on an empty stomach 1 hour before or 2 hours after eating and should be swallowed whole.
After oral capsule administration, the Cmax and AUC values exhibit marked intra- and inter-subject variability. Absorption site unknown.
BCS class 2
Drug interaction with antioxidant: Vitamin C and E (high dose)
Not enough information available to conclude on absorption after RYGB Risk of decreased efficiency due to Vitamin C and E supplementation
Drouard S, Vigneron J, May I. Traitement par étoposide oral : présentation adaptée à une meilleure observance pédiatrique hospitalière. Journal de Pharmacie Clinique. 18 oct 1999;18(3):251-7. McLeod HL, Relling MV. Stability of etoposide solution for oral use. Am J Hosp Pharm. nov 1992;49(11):2784‑5.
Fine-Shamir N, Beig A, Dahan A. Adequate formulation approach for oral chemotherapy: Etoposide solubility, permeability, and overall bioavailability from cosolvent- vs. vitamin E TPGS-based delivery systems. International Journal of Pharmaceutics. 15 mars 2021;597:120295
Film-coated tablet that should be swallowed whole and taken after a meal.
Food increases its bioavailability by 40%. Absorption site unknown.
Weak base Lipophilic molecule : Log P = 3.4 BCS class 2
Case report : 35 years old woman diagnosed with stage IIA , estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and HER-2-negative breast cancer - underwent left mastectomy followed by chemotherapy and then was switched to Exemestane. Then underwent laparoscopic Roux-en-Y gastric bypass at age 43 → About 4 weeks after her bariatric surgery, local recurrence of breast cancer and then metastatic disease. She has received multiple lines of therapy and has been doing well.
Lipophilic molecule → risk of altered absorption.
Zhang S, Ikramuddin S, Beckwith HC, Sheka AC, Wirth KM, Blaes AH. The Impact of Bariatric Surgery on Breast Cancer Recurrence: Case Series and Review of Literature. Obes Surg. févr 2020;30(2):780-5.
Hard capsules that should be swallowed whole. Administration with a high fat meal may reduce the incidence of nausea and vomiting and thus fedratinib is recommended to be taken with food.
A low-fat, low-calorie or a high-fat, high-calorie meal increased AUCinf up to 24% and Cmax up to 14% of a single 500 mg dose of fedratinib. Absorption site unknown.
Weak base - exhibits pH-dependent aqueous solubility permeability in vitro
Severe adverse event: Wernicke's encephalopathy is a neurological emergency resulting from a thiamine (vitamin B1) deficiency. Caution in RYGB patients with vitamin deficiencies.
pH-dependent solubility → risk of altered absorption - Severe adverse event : Wernicke's encephalopathy resulting from a vitamin B1 deficiency → caution with RYGB patients with vitamin deficiencies.
Film-coated tablets that should be swallowed whole with or without food
Bioavailability is not affected by high fat meal, but absorption is delayed Absorption site unknown
Hydrophilic molecule Log P = -2.8 BCS classification unknown
Few absorption modification due to RYGB
Plosker GL, Figgitt DP. Oral fludarabine. Drugs. 2003;63(21):2317-23.
Film-coated tablets that should be swallowed whole with a glass of water, with a meal
No relevant information Absorption site unknown
BCS class 2
Not enough information to conclude on absorption after RYGB
Ige PP, Badgujar RR, Nerkar PP, Mahajan HS, Sonawane RO, Surana SJ. Study of physicochemical properties of flutamide-loaded Ocimum basilicum microspheres with ex vivo mucoadhesion and in vitro drug release. Particulate Science and Technology. 4 juill 2018;36(5):583-91.
Film-coated tablets that may be administered as a dispersion in water (dropped in half a glass of water and swirled occasionally, until the tablet is dispersed) and may be taken with or without food.
Exposure to gefitinib is not significantly altered by food Absorption site unknown
Solubility increases with decreasing pH Highly lipophilic drug: Log P = 3.75 BCS class 2
pH-dependent solubility and lipophilic drug → risk of decreased absorption → tablets may be administered as a dispersion in water
Film-coated tablets that should be swallowed whole with or without food
Gilteritinib Cmax and AUC decreased by approximately 26% and less than 10%, respectively, when a single 40 mg dose of gilteritinib was co-administered with a high fat meal compared to gilteritinib exposure in fasted state. Median Tmax was delayed 2 hours when gilteritinib was administered with a high-fat meal Absorption site unknown
Solubility decreases as pH increase Highly lipophilic drug: log p = 4.35 BCS class 4
pH-dependent solubility and highly lipophilic drug → risk of decreased absorption
Film-coated tablets that should be swallowed whole with or without food
Administration of glasdegib with a high-fat, high-calorie meal resulted in 16% lower exposure (AUCinf) compared to overnight fasting. Absorption site unknown
Solubility decreases with increasing pH Predicted to be a lipophilic molecule log P in vitro: (calculated LogP = 2.28) BCS class 4
pH-dependent solubility and lipophilic drug → risk of decreased absorption
Shaik N, Hee B, Wei H, LaBadie RR. Evaluation of the effects of formulation, food, or a proton-pump inhibitor on the pharmacokinetics of glasdegib (PF-04449913) in healthy volunteers: a randomized phase I study. Cancer Chemother Pharmacol. mars 2019;83(3):463-72.
Hard capsules that should be swallowed whole, with a glass of water with or without food. Possible opening of the capsules with special precautions. Oral solution (Xromi®) off label - oral solution preparation
Rapidly absorbed by the digestive mucosa Absorption site unknown
Hydrophilic drug: log P = -1.80
Drug interaction: vitamin E supplementation may increase the risk of bleeding 5,700/µL pre-operatively and the nadir was 1,800/µL one year after the surgery while on a stable dose of hydroxyurea Case report : sickle cell disease and sleeve gastrectomy → Her neutrophil count was
Few absorption modifications due to RYGB
Heeney MM, Whorton MR, Howard TA, Johnson CA, Ware RE. Chemical and functional analysis of hydroxyurea oral solutions. J Pediatr Hematol Oncol. mars 2004;26(3):179-84.
Kabiche D, Balde IB, Majoul E, Kabiche S, Bourguignon E, Fontan JE, et al. Stability of Extemporaneously Prepared Hydroxycarbamide Oral Suspensions. Int J Pharm Compd. avr 2017;21(2):160-3.
Hard capsules that should be swallowed whole with or without food
Administration of ibrutinib in fasted condition resulted in approximately 60% of exposure (AUClast) as compared to either 30 minutes before, 30 minutes after (fed condition) or 2 hours after a high fat breakfast Absorption site unknown
Solubility decreases with increasing pH Very lipophilic drug: Log P= 3.97 BCS Class 2
Drug interaction: vitamin E supplementation may increase the risk of bleeding
pH-dependent solubility and lipophilic drug → risk of decreased absorption
Hard capsules that should be swallowed whole during a light meal
Absorption site unknown
Highly lipophilic drug: Log P =13.08 BCS Class 1
Antacids reduce the digestive absorption of Zavedos®: therefore, the concomitant association should be avoided.
Highly lipophilic drug → risk of altered absorption
Buckley MM, Lamb HM. Oral idarubicin. A review of its pharmacological properties and clinical efficacy in the treatment of haematological malignancies and advanced breast cancer. Drugs Aging. juill 1997;11(1):61-86.
Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev. nov 2016;50:247-63.
Film-coated tablets that should be swallowed whole with or without food
Administration with a high-fat meal resulted in no change in Cmax and a 36% increase in mean AUCinf. Absorption site unknown
pH-dependent solubility with superior solubility at low pH BCS Class 2
pH-dependent solubility → risk of altered absorption
Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev. nov 2016;50:247-63.
Hard capsules that may be dispersed in a glass of still water or apple juice with a meal and a large to minimize the risk of gastrointestinal irritations Oral solution available.
With a high-fat meal, the rate of absorption of imatinib was minimally reduced (11% decrease in Cmax and prolongation of tmax by 1.5 h), with a small reduction in AUC (7.4%) compared to fasting conditions. Absorbed in the small intestine (ileum major absorption site).
pH-dependent solubility Lipophilic molecule: log P = 1.99 Could be classified as BCS class I
Cases reports: A 36-year-old, morbidly obese woman with chronic myeloid leukemia imatinib 400mg/day → A complete molecular response was achieved with imatinib. Four years later, she underwent a sleeve gastrectomy while receiving imatinib -> The imatinib pharmacokinetic values during the year after sleeve gastrectomy were lower than the pharmacokinetic values before surgery, and indicate decreased absorption of imatinib but a complete molecular response was maintained.
A 54-year-old woman with chronic phase CML treated with imatinib at 400 mg daily underwent laparoscopic biliopancreatic diversion with duodenal switch, concomitant cholecystectomy -> after the surgery she experiences increased BCR–ABL and decreased plasmatic levels of imatinib -> imatinib dose was increased to 400mg BID and then 600mg BID -> any bariatric surgery or procedure that results in reducing gastric size and/or bypassing part of the small intestine may influence imatinib absorption that may be further exacerbated by diarrhea and/or weight loss, which may result in a marked reduction of imatinib levels
pH-dependent solubility and lipophilic drug and case report → risk of decreased absorption → oral solution can be used
Kralj E, Žakelj S, Trontelj J, Roškar R, Černelč P, Kristl A. Absorption and elimination of imatinib through the rat intestine in vitro. International Journal of Pharmaceutics. 2 janv 2014;460(1):144-9. Liu H, Artz AS. Reduction of imatinib absorption after gastric bypass surgery. Leuk Lymphoma. févr 2011;52(2):310-3.
Pavlovsky C, Egorin MJ, Shah DD, Beumer JH, Rogel S, Pavlovsky S. Imatinib mesylate pharmacokinetics before and after sleeve gastrectomy in a morbidly obese patient with chronic myeloid leukemia. Pharmacotherapy. sept 2009;29(9):1152
Film-coated tablets that should be swallowed whole with or without food
Following administration of a single dose in healthy subjects, a high-fat meal increased ivosidenib Cmax by 98% and AUCinf by approximately 25% Absorption site unknown
pH-independent solubility BCS class 2
Few absorption modification due to RYGB
Hard capsules that should be swallowed whole, at least 1 hour before or at least 2 hours after food
Administration with a high-fat meal decreased ixazomib AUC by 28% compared with administration after an overnight fast Absorption site unknown
The solubility increases as the pH increases Weakly basic (pKa = 8.5) and lipophilic drug: log P= 2.07 BCS Class 3
Drug interaction: vitamin E supplementation may increase the risk of bleeding
pH-dependent solubility and lipophilic drug → risk of decreased absorption
Film-coated tablets that should be swallowed whole at least one hour before or at least one hour after food
Depending on type of food the bioavailability is approximately 2-3 times higher when lapatinib is taken 1 hour after food compared with 1 hour before the first meal of the day Absorbed in the small intestine
Solubility decreases as pH increases (Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease) Very lipophilic molecule: calculated Log P = 5
Drug interaction with antioxidant: Vitamin C and E (high dose)
Lipophilic drug, absorption in the small intestine-> risk of altered absorption
Koch KM, Reddy NJ, Cohen RB, Lewis NL, Whitehead B, Mackay K, et al. Effects of Food on the Relative Bioavailability of Lapatinib in Cancer Patients. J Clin Oncol. 10 mars 2009;27(8):1191-6.
Morikawa A, Peereboom DM, Thorsheim HR, Samala R, Balyan R, Murphy CG, et al. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study. Neuro Oncol. févr 2015;17(2):289-95.
Hard capsules that should be swallowed whole with or without food Oral solution (capsule or oral solution with equivalent oral bioavailability and may be used interchangeably)
Larotrectinib Cmax was reduced by approximately 35% and there was no effect on AUC in healthy subjects administered VITRAKVI after a high-fat and high-calorie meal compared to the Cmax and AUC after overnight fasting. Absorption site unknown
pH-dependent solubility formal assessment of biopharmaceutical class has not been performed, larotrectinib sulfate has the attributes of a BCS Class 1 compound
pH-dependent solubility -> risk of altered absorption -> oral solution can be used
Hard capsules that should be swallowed whole with or without food
Co-administration with a high-fat and high-calorie meal in healthy volunteers reduces the extent ofabsorption, resulting in an approximately 20% decrease in area under the concentration versus time curve (AUC) and 50% decrease in Cmax in plasma Absorption site unknown
Moderate solubility at physiological pH where it is not ionized. In acidic conditions, such as in the stomach and proximal intestine, lenalidomide becomes protonated and its solubility increases greater than tenfold. Hydrophilic drug: log P= -0.4 BCS class 1
pH-dependent solubility → risk of altered absorption
Rozewski DM, Herman SEM, Towns WH, Mahoney E, Stefanovski MR, Shin JD, et al. Pharmacokinetics and tissue disposition of lenalidomide in mice. AAPS J. déc 2012;14(4):872-82.
Hard capsules that may be added without breaking or crushing them to a tablespoon of water or apple juice in a small glass to produce a suspension Lenvatinib may be taken with or without food.
Food does not affect the extent of absorption, but slows the rate of absorption. When administered with food to healthy subjects, peak plasma concentrations are delayed by 2 hours
Solubility decreasing from very slightly soluble to practically insoluble as pH increases The Applicant did not submit necessary information for BCS classification. It is unknown if it is BCS class 2 or 4
Drug interaction: vitamin E supplementation may increase the risk of bleeding
pH-dependent solubility → risk of altered absorption, lenvatinib capsules may be added without breaking or crushing them to a tablespoon of water or apple juice in a small glass to produce a suspension - Vitamine E supplementation → monitor the increased risk of bleeding
Film-coated tablets that should be swallowed whole with or without food
Food ingestion slightly decreases the rate of absorption: Tmax increased and Cmax decreased but does not modify the degree of absorption (AUC). Absorption site unknown
Lipophilic drug: log P = 2.5 BCS class 1
Lipophilic drug → risk of altered absorption
Hard capsules that should be swallowed whole in the evening or 3 hours after a meal.
No relevant information Absorption site unknown
It is relatively un-ionized at a physiological pH. Because of the high lipid solubility and the relative lack of ionization at physiological pH, lomustine crosses the blood-brain barrier quite effectively. Lipophilic drug: Log P = 2.83 Unknown if it's BCS class 2 or 4
pH-dependent solubility and lipophilic drug → risk of decreased absorption
Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev. nov 2016;50:247-63.
Film-coated tablets that should be swallowed whole with or without food
Administration of lorlatinib with a high fat, high calorie meal resulted in 5% higher exposure compared to fasted conditions. The high concentration in the stomach and small intestines suggested that lorlatinib was primarily absorbed by the stomach and small intestines.
The aqueous solubility of lorlatinib is high at low pH and decreases with increasing pH. It has very low solubility above pH 4.5. BCS class 4
pH-dependent solubility - stomach and small intestine absorption → risk of decreased absorption
Chen W, Shi Y, Qi S, Zhou H, Li C, Jin D, et al. Pharmacokinetic Study and Tissue Distribution of Lorlatinib in Mouse Serum and Tissue Samples by Liquid Chromatography-Mass Spectrometry. J Anal Methods Chem. 2019;2019:7574369.
Film-coated tablets that should be swallowed whole 15 to 30mns before a meal
Simultaneous ingestion of food delays Tmax and decreases the area under the curve by approximately 39-45%. Absorption site unknown
Solubility is known to decrease under alkaline pH conditions Hydrophilic molecule: Log P = -0.52 Unknown if it's BCS class 2 or 4
Drug interaction: vitamin E supplementation may increase the risk of bleeding
pH-dependent solubility → risk of altered absorption Vitamin E supplementation → monitor the increased risk of bleeding
Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev. nov 2016;50:247-63.
Kitazawa F, Kado Y, Ueda K, Kokufu T, Fuchida SI, Okano A, et al. The interaction between oral melphalan and gastric antisecretory drugs: Impact on clinical efficacy and toxicity. Mol Clin Oncol. févr 2016;4(2):293-7.
Tablets that should be swallowed whole on an empty stomach - crushing the tablets is exceptionally possible extemporaneously (CNHIM) Xaluprine® oral suspension - Oral suspension preparation
The mean Cmax with the oral suspension was 39% higher than the tablet although there was less between-subject variability with the oral suspension (46%) than the tablet (69%). Prodrug that requires intestinal absorption - small intestine
Hydrophilic drug Log P = 0.01 BCS class 2
Absorption in small intestine → risk of altered absorption
Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev. nov 2016;50:247-63.
Xu LL, Chen JM, Yan Y, Lu TB. Improving the Solubility of 6-Mercaptopurine via Cocrystals and Salts. Crystal Growth & Design. 5 déc 2012;12(12):6004-11.
Aliabadi HM, Romanick M, Desai S, Lavasanifar A. Effect of buffer and antioxidant on stability of a mercaptopurine suspension. Am J Health Syst Pharm. 1 mars 2008;65(5):441-7.
Pennington AM, Bronk JR. The absorption of 6-mercaptopurine from 6-mercaptopurine riboside in rat small intestine: effect of phosphate. Cancer Chemother Pharmacol. 1995;36(2):136-42.
Peacock GF, Sauvageot J, Hill A, Killian A. Evaluation of the Stability of Mercaptopurine Suspension Compounded in a Commercial Vehicle and the Determination of an Appropriate Beyond-use Date. Int J Pharm Compd. févr 2016;20(1):81-5.
Tablets that should be swallowed whole with or without food
Increased bioavailability if taken before meals Absorbed in the small intestine
pH dependent solubility BS Class 4
pH-dependent solubility, lipophilic drug and absorption in small intestine → high risk of decreased absorption
dos Santos AM, Carvalho FC, Teixeira DA, Azevedo DL, de Barros WM, Gremião MPD. Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation. International Journal of Pharmaceutics. 30 mai 2017;524(1):330-8.
Giri BR, Kim JS, Park JH, Jin SG, Kim KS, Din FU, et al. Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium. Pharmaceutics. 16 janv 2021;13(1):111.
Friedman B, Cronstein B. Mécanisme d'action du méthotrexate dans le traitement de la polyarthrite rhumatoïde. Rev Rhum Ed Fr. mars 2020;87(2):92-8
Soft capsules that should be swallowed whole with food
Midostaurin absorption (AUC) was increased by an average of 22% when Rydapt® was co-administered with a standard meal and by an average of 59% when co-administered with a high-fat meal. Peak midostaurin concentration (Cmax) was reduced by 20% with a standard meal and by 27% with a high-fat meal versus on an empty stomach Absorption site unknown
BCS class 2 High permeability, relatively high lipophilicity
Drug interaction with antioxidant: Vitamin C and E (high dose)
Relatively high lipophilicity → risk of altered absorption
Tablets that should be swallowed whole - possibility of reducing to powder (off-label use). Mix with yoghurt or high fat product because lipophilic drug - do not mix with water
Absorption site unknown
Highly lipophilic drug: Log P = 6 Unknown if it's BCS class 2 or 4
Drug interaction: vitamin E supplementation may increase the risk of bleeding - Fat tissue can act as a reservoir for mitotane, resulting in a prolonged half-life and potential accumulation of mitotane → Caution and close monitoring of mitotane plasma levels are highly recommended when treating overweight patients.
Very lipophilic drug - Caution with patient after RYGB because Mitotane should preferably be taken during meals containing fat-rich food -> risk of altered absorption
Haider MS, Ahmad T, Groll J, Scherf-Clavel O, Kroiss M, Luxenhofer R. The Challenging Pharmacokinetics of Mitotane: An Old Drug in Need of New Packaging. Eur J Drug Metab Pharmacokinet. sept 2021;46(5):575-93.
Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev. nov 2016;50:247-63.
Hard capsules that should be swallowed whole with water - the content of each hard capsule may bedispersed in one teaspoon of apple sauce (apple compote) and should be taken immediately. Nilotinib must be taken without food (2hours after or 1h before a meal).
BCS class 4 Absorption site unknown
pH-dependent solubility, with lower solubility at higher pH Highly lipophilic (calculated LogP= 4.8)
Case report: A 30 year old morbidly obese male underwent Gastric sleeve gastrectomy, two years later diagnosed with chronic myeloid leukemia → started on Nilotinib 300 mg BID → achieved complete hematological response but failed cytogentic and molecular response mutation analysis tends to be negative. Shifted to Imatinib where he achieved hematological, cytogentics and molecular response
pH-dependent solubility and highly lipophilic drug → high risk of decreased absorption → the content of each hard capsule may be dispersed in one teaspoon of apple sauce (apple compote)
Yassin MA, Nashwan A, Kassem N. Second Generation Tyrosisne Kinase Inhibitors As Upfront Therapy in the Era of Sleeve Gastrectomy Does It Work? Blood. 8 déc 2017;130:5260.
Xia B, Heimbach T, He H, Lin T han. Nilotinib preclinical pharmacokinetics and practical application toward clinical projections of oral absorption and systemic availability. Biopharm Drug Dispos. déc 2012;33(9):536-49.
Hard capsules that should be swallowed whole with or without food
A concomitant high-fat meal did not significantly affect the pharmacokinetics of niraparib after administration of 300 mg of niraparib. Absorption site unknown
pH-independent solubility BCS Class 2
Few absorption modification expected due to RYGB
Tablets that must be swallowed whole (tablets can be crushed, or cut extemporaneously (however the laboratory does not recommend administration by gastric tube). Tablets can be taken with or without food.
Absorption site unknown
Lipophilic drug: log P = 1.8 BCS Class unknown
Lipophilic drug → risk of altered absorption
Film-coated tablets that should be swallowed whole with or without food.
Co-administration with food slowed the rate (Tmax delayed by 2.5 hours and Cmax reduced by approximately 21%) but did not significantly affect the extent of absorption of olaparib (AUC increased 8%) Absorption site unknown
pH independent solubility BCS class 4
Few absorption modification expected due to RYGB
Film-coated tablets that should be swallowed whole (the tablet may first be dispersed in 50 mL of non-carbonated water. It should be dropped in the water, without crushing, stirred until dispersed and immediately swallowed) with or without food.
Food does not alter osimertinib bioavailability to a clinically meaningful extent. Absorption site: small intestine
pH-dependent aqueous solubility BCS class 3
pH-dependent solubility -> risk of altered absorption -> the tablet may be dispersed in 50 mL of non-carbonated water Absorption in small intestine -> risk of altered absorption
Kawaguchi Y, Hanaoka J, Hayashi H, Fukuda Y, Iihara H, Suzuki A, et al. Clinical efficacy of osimertinib for a patient with ileus due to peritoneal carcinomatosis. Clin Case Rep. 3 janv 2020;8(2):347-50.
Hard capsules that should be swallowed whole with or without food
There was no significant effect of food on the pharmacokinetics of pacritinib Absorption site unknown
pH dependent solubility → low solubility at physiological pH but higher at acidic pH Should be considered as BCS class 3/4.
pH-dependent solubility → risk of altered absorption
Hard capsules that should be administered in the fasting state - capsules can be opened- dissolution in apple juice or apple compote (CNHIM)
Administration with food → 33 % decrease in Cmax and a 9 % decrease in area under the curve (AUC)
Administration with ranitidine → did not result in alterations in the extent of absorption of temozolomide
or the exposure to its active metabolite
Absorption site unknown but readily absorbed in the small intestine
Temozolomide is unionized and does not show any pH dependant solubility.
Log P = -1.153
BCS class 1
A 52-year-old man with a historic of Roux-en-Y gastric bypass was treated by TMZ 190 mg for a glioblastoma → progression of disease → pharmacokinetics study → progression of this patient’s disease on temozolomide therapy was likely not due to reduced absorption and inadequate plasma concentrations of temozolomide, but probably reflected inherent resistance of his tumor to temozolomide therapy
Few absorption modifications due to RYGB.
Wesolowski JR, Rajdev P, Mukherji SK. Temozolomide (Temodar). AJNR Am J Neuroradiol. sept 2010;31(8):1383-4. Park DM, Shah DD, Egorin MJ, Beumer JH. Disposition of temozolomide in a patient with glioblastoma multiforme after gastric bypass surgery. J Neurooncol. juin 2009;93(2):279-83.
Film-coated tablets that should be swallowed whole and taken with a meal.
Administration with a low-fat meal → increased venetoclax exposure by approximately 3.4-fold
Administration with a high-fat meal → increased venetoclax exposure by 5.1- to 5.3-fold compared tofasting
conditions - Gastric acid reducing agents do not affect venetoclax bioavailability
Absorption site unknown
Weak base with low and pH-dependent aqueous solubility with somewhat higher solubility at pH 1 and 12, and
lower solubility at pH 4 and 7
Lipophilic drug : log P = 5.5
BCS class 4
Lipophilic molecule and pH dependent solubility → risk of decreased absorption
Off label possible use of Venetoclax 25 mg orodispersible tablets (AAC)
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