Document Detail

Stereoselectivity in the hydroxylation of propafenone enantiomers in mouse hepatic microsomes.
MedLine Citation:
PMID:  8069263     Owner:  NLM     Status:  MEDLINE    
Stereoselectivity in the oxidative metabolism of propafenone (PPF) enantiomers to 5-hydroxypropafenone was studied with untreated and inducer-treated mouse hepatic microsomes. In the untreated microsomes, Lineweaver-Burk plots of the 5-hydroxylation of R(-)- and S(+) PPF. single lines, and the intrinsic clearance (Vmax/Km) value of R(-)-PPF was 1.3-fold higher than that of S(+)-PPF. When racemic PPF was used as a substrate, the plot was shifted to the upper region, in comparison with that estimated from the sum of the individual 5-hydroxylase activities of each enantiomer, suggesting enantiomer/enantiomer interaction. In phenobarbital-induced microsomes, the Lineweaver-Burk plot for R(-)-PPF was a single line, but that for S(+)-PPF was biphasic. When racemic PPF was used as a substrate, the plot was biphasic and was shifted to the upper region in comparison with that estimated from the sum of the individual 5-hydroxylase activities of each enantiomer. The observed value of intrinsic clearance of the PPF racemate at lower concentrations (Vmax/Km1) was consistent with the estimated value, suggesting no interaction between R(-)- and S(+)-PPF. These findings indicate that most of the 5-hydroxylation of R(-)- and S(+)-PPF is catalyzed by common cytochrome P-450 species, but a part of S(+)-PFF 5-hydroxylation is catalyzed by another phenobarbital inducible cytochrome P-450 species, particularly at lower substrate concentrations.
K Morita; M Mizuochi; A Yamaji; T Yokoyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  17     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-09-26     Completed Date:  1994-09-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  531-4     Citation Subset:  IM    
Department of Hospital Pharmacy, Shiga University of Medical Science, Ohtsu, Japan.
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MeSH Terms
Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme System / metabolism
Microsomes, Liver / drug effects,  metabolism*
Phenobarbital / pharmacology
Propafenone / analogs & derivatives,  metabolism*
Reg. No./Substance:
50-06-6/Phenobarbital; 54063-53-5/Propafenone; 86384-10-3/5-hydroxypropafenone; 9035-51-2/Cytochrome P-450 Enzyme System

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