Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects.
Clin Pharmacol Drug Dev
; 7(4): 435-440, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29058801
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 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfonamides
/
Bridged Bicyclo Compounds, Heterocyclic
/
Proto-Oncogene Proteins c-bcl-2
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Clin Pharmacol Drug Dev
Year:
2018
Document type:
Article