The role of lipophilicity in the inhibition of polymorphic cytochrome P450IID6 oxidation by beta-blocking agents in vitro

doi:10.1016/0024-3205(91)90341-8

Life Sciences

Volume 48, Issue 23, 1991, Pages 2259-2265

https://doi.org/10.1016/0024-3205(91)90341-8 Get rights and content

Abstract

The importance of lipophilicity as a determinant of the affinity of betaadrenoceptor blocking agents for a specific human hepatic monooxygenase — cytochrome P450IID6 (responsible for the debrisoquine-type of oxidation polymorphism) — was investigated in vitro by estimating the inhibition constants of a series of compounds in a microsomal system with monitoring of the kinetics of dextromethorphan O-demethylation. Lipophilicity is a key predictor of the affinity of beta-blocking drugs for cytochrome P450IID6 and of their potential to cause specific competitive drug interactions, but more complex structural factors appear to be important as well. A high lipophilicity is also a necessary, but not a sufficient condition for these compounds to be metabolized by cytochrome P450IID6.

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The role of lipophilicity in the inhibition of polymorphic cytochrome P450IID6 oxidation by beta-blocking agents in vitro

Abstract

Am. Heart J.

Pharmacol. Ther.

Anal. Biochem.

Eur. J. Pharmacol.

Biochem. Pharmacol.

J. Pharm. Sci.

J. Pharm. Sci.

Pharmacol. Res. Commun.

Life Sci.

Biochem. Pharmacol.

Biochem. Biophys. Res. Commun.

J. Am. Chem. Soc.

Pharmacol. Ther.

Drug Metab. Rev.

J. Pharmacokinet. Biopharm.

Clin. Pharmacokinet.

Eur. J. Clin. Pharmacol.

J. Cardiovasc. Pharmacol.