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

Ahmed Hamed Salem*, Suresh K. Agarwal, Martin Dunbar, Silpa Nuthalapati, David Chien, Kevin J. Freise, Shekman L. Wong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Venetoclax is a selective, first-in-class, B-cell lymphoma-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 with 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 2 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 affect bioavailability. The median Tmaxof venetoclax was delayed by about 2 hours when administered with food. Compared with fasting conditions, Cmaxand AUC increased by approximately 3.4-fold following a low-fat breakfast. High-fat meals increased Cmaxand 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 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.

Original languageEnglish
Pages (from-to)1355-1361
Number of pages7
JournalJournal of Clinical Pharmacology
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • BCL-2
  • CLL
  • NHL
  • bioavailability
  • fat
  • food effect
  • pharmacokinetics
  • venetoclax

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