The role of lipophilicity in the inhibition of polymorphic cytochrome P450IID6 oxidation by beta-blocking agents in vitro.
Article Details
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Ferrari S, Leemann T, Dayer P
The role of lipophilicity in the inhibition of polymorphic cytochrome P450IID6 oxidation by beta-blocking agents in vitro.
Life Sci. 1991;48(23):2259-65.
- PubMed ID
- 1675413 [ View in PubMed]
- Abstract
The importance of lipophilicity as a determinant of the affinity of beta-adrenoceptor 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Pindolol Cytochrome P450 2D6 Protein Humans UnknownSubstrateInhibitorDetails