Drug−drug Interaction between Losartan and Paclitaxel in Human Liver Microsomes with Different CYP 2C8 Genotypes

The cytochrome P450 ( CYP ) 2C8*3 allele is associated with reduced metabolic activity of paclitaxel. This study was aimed to investigate the inhibitory effect of losartan on paclitaxel metabolism in human liver microsomes ( HLM s) and to determine the impact of the CYP 2C8*3 polymorphism. HLM s that contained the CYP 2C8*1 homozygote ( HL 60) or CYP 2C8*3 heterozygote ( HL 54) genotype were used for the inhibition study. Losartan, at a concentration of 50 μmol/L, significantly inhibited paclitaxel metabolism by 29% and 57% in the HL 60 ( p