Plasma pharmacokinetics and CYP3A12-dependent metabolism of c-kit inhibitor imatinib in dogs
作者： M. Ishizuka , S. Nagai , K. Q. Sakamoto , S. Fujita
DOI: 10.1080/00498250600962849
关键词:
摘要: Imatinib is a highly selective tyrosine kinase inhibitor, and used for the treatment of chronic myeloid leukaemia (CML) gastrointestinal stromal tumours (GISTs) in humans. The aim this study to determine vitro vivo pharmacokinetics imatinib dogs which cytochrome P450 (CYPs) contribute its metabolism. was administered orally or intravenously time peak concentration (T(max)) 4-9 h. mean half-life 622 +/- 368 min, AUC 1256 809 microM * min after oral administration. range C0 injected 12-24 microM. intravenous injection were 206 112 1026 371 respectively. Recombinant system dog CYP3A12 CYP2C21 showed that contributed metabolism imatinib. inhibition CYP3A-dependent activity using rat anti-CYP3A antibody ketoconazole revealed plays major role liver microsomes.
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