Effect of Low and High Fat Meals on the Pharmacokinetics of Venetoclax, a Selective First-in-Class Bcl-2 Inhibitor.

Venetoclax is a selective, first-in-class, Bcl-2 inhibitor that has demonstrated clinical efficacy in several hematological malignancies. Two studies evaluated the relative bioavailability of venetoclax in healthy subjects: 1) a bioequivalence study to compare the bioavailability of the film-coated tablet to that of an earlier uncoated tablet and 2) a food effect study to evaluate the effect of food on venetoclax pharmacokinetics. Both studies were open-label, single-dose, crossover studies. In the bioequivalence study, 15 subjects received a single dose of venetoclax 50 mg under nonfasting conditions in each of two periods; one period used the uncoated tablet and the other used the film-coated tablet. In the food effect study, 24 subjects received a single dose of venetoclax film-coated 100 mg tablet under fasting conditions, after a low-fat breakfast, or after a high-fat breakfast in different periods. The venetoclax film-coated tablet was bioequivalent to the uncoated tablet which indicates that the film coating does not impact the bioavailability. Median Tmax of venetoclax was delayed by about 2 hours when administered with food. Compared to fasting conditions, Cmax and AUC increased by approximately 3.4-fold following a low-fat breakfast. High-fat meals increased Cmax and AUC by approximately 50% relative to low fat meals. The mean terminal half-life was comparable between the high-fat meal and fasting conditions (19.1 hours versus 16.1 hours). Based on these results and the venetoclax exposure-response profile, venetoclax should be administered with food, and without specific recommendations for fat content, to ensure adequate and consistent bioavailability. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!