Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects.

Journal Article (Journal Article)

Venetoclax has been approved in the United States, Europe, Canada, and Australia for appropriate patients with difficult-to-treat chronic lymphocytic leukemia (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve healthy first-generation Han Chinese subjects received a single 100-mg dose of venetoclax following a low-fat breakfast. Pharmacokinetic parameters were estimated using noncompartmental methods. After a single dose of venetoclax in healthy Chinese subjects, the median time to peak concentration was 6 hours (range, 4 to 6 hours), and the mean ± SD Cmax , AUCinf , and terminal half-life were 1.0 ± 0.32 μg/mL, 12.6 ± 5.4 μg·h/mL, and 18.4 ± 2.97 hours, respectively. On average, venetoclax Cmax and AUCinf values were 94% and 66% higher, respectively, in Chinese subjects compared with those observed historically for non-Asian subjects receiving the same dose. Based on these pharmacokinetic results and the established exposure-response relationship of venetoclax in non-Asian CLL subjects, a 400-mg once-daily dosage regimen was selected for evaluating the venetoclax pharmacokinetics, efficacy, and safety in the venetoclax phase 2 open-label study in Chinese subjects with R/R CLL.

Full Text

Duke Authors

Cited Authors

  • Cheung, TT; Salem, AH; Menon, RM; Munasinghe, WP; Bueno, OF; Agarwal, SK

Published Date

  • May 2018

Published In

Volume / Issue

  • 7 / 4

Start / End Page

  • 435 - 440

PubMed ID

  • 29058801

Electronic International Standard Serial Number (EISSN)

  • 2160-7648

Digital Object Identifier (DOI)

  • 10.1002/cpdd.395

Language

  • eng

Conference Location

  • United States