Title : In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors.

Pub. Date : 1996

PMID : 8737761






5 Functional Relationships(s)
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1 METHODS: Affinity was determined as the inhibitory potency for prototype reactions for 3 major drug metabolising enzymes: diclofenac 4"-hydroxylation (CYP2C9), dextromethorphan O-demethylation (CYP2D6), and midazolam 1"-hydroxylation (CYP3A4). Diclofenac cytochrome P450 family 2 subfamily C member 9 Homo sapiens
2 Racemic and (+)- and (-)-fluvastatin showed moderate affinity (estimated Ki > 50 micromol.1(-1)) for CYP2D6 and CYP3A4, whereas their affinity for CYP2C9 was high (estimated Ki < 1 micromol.1(-1)). (+)- and (-)-fluvastatin cytochrome P450 family 2 subfamily C member 9 Homo sapiens
3 CONCLUSION: Fluvastatin selectively inhibits a major drug metabolising enzyme (CYP2C9), the (+)-isomer (pharmacologically more active) showing 4-5 fold higher affinity. Fluvastatin cytochrome P450 family 2 subfamily C member 9 Homo sapiens
4 As already reported for lovastatin and simvastatin, in vivo drug interactions by inhibition of liver oxidation of CYP2C9 substrates (e.g. hypoglyceamic sulphonylureas and oral anticoagulants) may be expected. Lovastatin cytochrome P450 family 2 subfamily C member 9 Homo sapiens
5 As already reported for lovastatin and simvastatin, in vivo drug interactions by inhibition of liver oxidation of CYP2C9 substrates (e.g. hypoglyceamic sulphonylureas and oral anticoagulants) may be expected. Simvastatin cytochrome P450 family 2 subfamily C member 9 Homo sapiens