Document Detail

The role of lipophilicity in the inhibition of polymorphic cytochrome P450IID6 oxidation by beta-blocking agents in vitro.
MedLine Citation:
PMID:  1675413     Owner:  NLM     Status:  MEDLINE    
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.
S Ferrari; T Leemann; P Dayer
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  48     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1991  
Date Detail:
Created Date:  1991-07-12     Completed Date:  1991-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2259-65     Citation Subset:  IM    
Division of Clinical Pharmacology, University Hospital, Geneva, Switzerland.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology*
Cytochrome P-450 Enzyme System / antagonists & inhibitors*,  metabolism
Dextromethorphan / metabolism
Dextrorphan / metabolism
Isoenzymes / antagonists & inhibitors*,  metabolism
Microsomes, Liver / enzymology
Oxidoreductases, O-Demethylating / antagonists & inhibitors*,  metabolism
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Isoenzymes; 125-71-3/Dextromethorphan; 125-73-5/Dextrorphan; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Oxidoreductases, O-Demethylating; EC 1.-/dextromethorphan O-demethylase

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