Study of the activity of P450 2D6 in organic solvents and of the potential inhibition of P450 enzymes by food supplements

We investigated the ability of CYP2D6 to catalyze dextromethorphan O-demethylation in acetonitrile, chloroform, cyclohexane, and dichloromethane. Interestingly, in acetonitrile 20% activity was recovered.We next carried in vitro studies on the inhibitory effect of nicotinic acid and nicotinamide on human P450s involved in drug metabolism (CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4). At their therapeutic level, nicotinic acid inhibits CYP2D6 (Ki = 19 +/- 4 mM) whereas nicotinamide inhibits CYP2D6 (Ki = 3.8 +/- 0.3 mM), CYP2E1 (Ki = 13 +/- 8 mM) and CYP3A4 (Ki = 13 +/- 3 mM).Finally, we have analyzed the different fractions (flavonoids and terpenoids) of a standardized Ginkgo biloba extract (EBG761) for their inhibition of the same human P450s as above. Our study shows that the flavonoidic fraction strongly inhibits these enzymes, especially CYP2C9 (Ki = 4.6 +/- 0.6 mM)