Losartan CYP2C9 substrate

In view of their incomplete oral bioavailability, several CYP2C substrates may undergo significant first-pass intestinal metabolism, including the CYP2C9 substrates verapamil (155), losartan (156), fluvastatin (157), and diclofenac (158), and the CYP2C19 substrates (5)-mephenytoin (159) and omeprazole... 

The interaction of losartan with phenytoin has been studied in a randomized, crossover study in 16 healthy volunteers (74). Losartan, a CYP2C9 substrate, had no effect on the pharmacokinetics of phenytoin. However, phenytoin inhibited the CYP2C9-mediated conversion of losartan to its active metabolite, thus potentially reducing its efficacy. 

Both phenytoin and losartan are substrates for the cytochrome P450 isoenzyme CYP2C9. It appears that phenytoin had an inhibitory effect on losartan metabolism. The conversion of losartan to E3174 represents about 5 to 15% of the clearance of an oral losartan dose, but E3174 is much more active than losartan. 

No significant effects on the drug-metabolizing isoenzyme CYP2C9 were observed in healthy volunteers orally administered 25 mg of losartan (a CYP2C9 substrate) before or after oral administration (average volunteer weight was 71 kg) of an aqueous extract 30 g of Chinese peony daily for 5 days (Xie et al. 2002). 

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