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

Tommy T. Cheung, Ahmed Hamed Salem*, Rajeev M. Menon, Wijith P. Munasinghe, Orlando F. Bueno, Suresh K. Agarwal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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 C max , AUC inf , 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 C max and AUC inf 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.

Original languageEnglish
Pages (from-to)435-440
Number of pages6
JournalClinical Pharmacology in Drug Development
Volume7
Issue number4
DOIs
StatePublished - May 2018
Externally publishedYes

Keywords

  • ABT-199
  • BCL-2
  • Chinese
  • pharmacokinetics
  • venetoclax

Fingerprint

Dive into the research topics of 'Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects'. Together they form a unique fingerprint.

Cite this