Population pharmacokinetics of imatinib mesylate in healthy Korean subjects

• Published in: Translational and clinical pharmacology Vol. 24; no. 2; pp. 96 - 104
• Main Authors: Park, Gab-jin, Park, Wan-Su, Bae, Soohyun, Park, Sung-min, Han, Seunghoon, Yim, Dong-Seok
• Format: Journal Article
• Language: English
• Published: 대한임상약리학회 2016
• Subjects: 의약학
• ISSN: 2289-0882; 2383-5427
• DOI: 10.12793/tcp.2016.24.2.96

Imatinib (GleevecTM; Novartis Pharmaceuticals) is an orally administered protein-tyrosine kinase in-hibitor. 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 first-order 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), inter-compartmental 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. KCI Citation Count: 0