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

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

  • 1991-01-01
Published in:
  • Life sciences. - 1991
Adrenergic beta-Antagonists
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Dextromethorphan
Dextrorphan
Humans
In Vitro Techniques
Isoenzymes
Microsomes, Liver
Oxidation-Reduction
Oxidoreductases, O-Demethylating
Solubility
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://roar.hep-bejune.ch/global/documents/39207
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