Population pharmacokinetics of imatinib mesylate in healthy Korean subjects

Gab-jin Park, Wan-Su Park, Soohyun Bae, Sung-min Park, Seunghoon Han, Dong-Seok Yim
2016 Translational and Clinical Pharmacology  
Imatinib (Gleevec TM ; 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
more » ... r 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. Methods Study design and data Data from 112 healthy male subjects, providing 1,773 blood samples in three different clinical trials, were merged for population PK analysis. The three comparative PK (reference versus test formulation) studies with open-labelled, randomized, 2×2 crossover design were conducted at the clinical trial center of Seoul St. Mary's hospital. Imatinib was administered orally at a single dose of 100 mg for 36 subjects in one study and 400 mg
doi:10.12793/tcp.2016.24.2.96 fatcat:pehzfsm3lfdsvpup2oxdxgg3wa