Population pharmacokinetics of imatinib mesylate in healthy Korean subjects.
10.12793/tcp.2016.24.2.96
- Author:
Gab Jin PARK
1
;
Wan Su PARK
;
Soohyun BAE
;
Sung Min PARK
;
Seunghoon HAN
;
Dong Seok YIM
Author Information
1. Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. yimds@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Imatinib;
population pharmacokinetics;
NONMEM;
Weibull
- MeSH:
Absorption;
Humans;
Imatinib Mesylate*;
Male;
Methods;
Pharmacokinetics*;
Plasma;
Protein-Tyrosine Kinases;
Volunteers
- From:Translational and Clinical Pharmacology
2016;24(2):96-104
- CountryRepublic of Korea
- Language:English
-
Abstract:
Imatinib (Gleevec™; Novartis Pharmaceuticals) is an orally administered protein-tyrosine kinase inhibitor. The goal of this study was to investigate the population pharmacokinetics (PK) of imatinib (as imatinib mesylate) in healthy male Koreans. A total of 1,773 plasma samples from 112 healthy male volunteers enrolled in three phase I clinical studies were used. Among the subjects, 76 received 400 mg and 36 received 100 mg as single oral doses. Peripheral blood sampling for PK analysis was done at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, 60 and 72 (at 400 mg group) h after dosing. The firstorder conditional estimation with interaction method of NONMEM® (ver. 7.3) was used to build the population PK model. A two-compartment model with Weibull absorption and elimination gave the best fit to the data. The estimates of clearance (CL/F), volume of central compartment (Vc/F), intercompartmental clearance (Q/F), peripheral volume (Vp/F) and their interindividual variabily (%CV) were 13.6 L/h (23.4%), 153 L (29.2%), 8.64 L/h (35.9%) and 64 L (67%), respectively.
