Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes.

ABSTRACT:

Background and purpose

Imatinib is a clinically important inhibitor of tyrosine kinases that are dysregulated in chronic myelogenous leukaemia and gastrointestinal stromal tumours. Inter-individual variation in imatinib pharmacokinetics is extensive, and influences drug safety and efficacy. Hepatic cytochrome P450 (CYP) 3A4 has been implicated in imatinib N-demethylation, but the clearance of imatinib decreases during prolonged therapy. CYP3A phenotype correlates with imatinib clearance at the commencement of therapy, but not at steady state. The present study evaluated the possibility that multiple CYPs may contribute to imatinib oxidation in liver.

Experimental approach

Imatinib biotransformation in human liver microsomes (n= 20) and by cDNA-expressed CYPs was determined b

SUBMITTER: Nebot N 

PROVIDER: S-EPMC2998687 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature