title: Effect of Low- and High-Fat Meals on the Pharmacokinetics of Venetoclax, a Selective First-in-Class BCL-2 Inhibitor.
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.
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc, North Chicago, IL, USA. ahmed.salem@abbvie.com.|Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. ahmed.salem@abbvie.com.
authors.forename: Ahmed Hamed
authors.initials: AH
authors.lastname: Salem
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc, North Chicago, IL, USA.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Agarwal
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc, North Chicago, IL, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Dunbar
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc, North Chicago, IL, USA.
authors.forename: Silpa
authors.initials: S
authors.lastname: Nuthalapati
authors.affiliation: Oncology Development, AbbVie Inc, North Chicago, IL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chien
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc, North Chicago, IL, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Freise
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie Inc, North Chicago, IL, USA.
authors.forename: Shekman L
authors.initials: SL
authors.lastname: Wong
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000097:blood* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D018752:Diet, Fat-Restricted / Q000379:methods; D059305:Diet, High-Fat / Q000379:methods; D004041:Dietary Fats / Q000097:blood*; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004041:Dietary Fats; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C579720:venetoclax
keywords: BCL-2; CLL; NHL; bioavailability; fat; food effect; pharmacokinetics; venetoclax