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Verapamil and drug metabolism by the cytochrome P450 isoform CYP1A2

Verapamil and drug metabolism by the cytochrome P450 isoform CYP1A2 Eur J Clin Pharmacol (1992) 42:463-464 European Journal of e @Q erle@ g (~[~[~(~(~ @ Springer-Verlag 1992 Letter to the editors U. Fuhr 1, B. G. Woodcock 1, and M. Siewert 2 Department of Clinical Pharmacology, University Hospital, Frankfurt/M. and Central Laboratory of German Pharmacists,Eschborn, FRG Received: June 5,1991/Accepted in revised form: September 9, 1991 Key words: Verapamil, Cytochrome P450; theophylline, CYP1A2, drug interaction A decrease in the clearance of theophylline when verapamil is co-administered [1] is a clinically relevant drug interaction involving hepatic cytochrome P450 isoforms [2]. Evidence obtained from mammalian cells genetically engineered to express a single cytochrome P450 isoform has shown that CYPIA2 is responsible for a major part of theophylline metabolism in man [Fuhr et al. unpublished observation]. Investigations have now been done in vitro to establish whether verapamil is an inhibitor of and a substrate for CYPIA2. was found, but only 4 data points were available for analysis. The 35% inhibition of caffeine 3-demethylation by verapamil clearly indicates that verapamil binds to CYP1A2, since no other isoenzyme is expected to contribute significantly to the 3-demethylation of caffeine under t- 100- o o_ c~ 80- ¢. 60- 40- Verapamil as an inhibitor of CYP1A2 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Clinical Pharmacology Springer Journals

Verapamil and drug metabolism by the cytochrome P450 isoform CYP1A2

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References (6)

Publisher
Springer Journals
Copyright
Copyright © 1992 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology
ISSN
0031-6970
eISSN
1432-1041
DOI
10.1007/BF00280138
Publisher site
See Article on Publisher Site

Abstract

Eur J Clin Pharmacol (1992) 42:463-464 European Journal of e @Q erle@ g (~[~[~(~(~ @ Springer-Verlag 1992 Letter to the editors U. Fuhr 1, B. G. Woodcock 1, and M. Siewert 2 Department of Clinical Pharmacology, University Hospital, Frankfurt/M. and Central Laboratory of German Pharmacists,Eschborn, FRG Received: June 5,1991/Accepted in revised form: September 9, 1991 Key words: Verapamil, Cytochrome P450; theophylline, CYP1A2, drug interaction A decrease in the clearance of theophylline when verapamil is co-administered [1] is a clinically relevant drug interaction involving hepatic cytochrome P450 isoforms [2]. Evidence obtained from mammalian cells genetically engineered to express a single cytochrome P450 isoform has shown that CYPIA2 is responsible for a major part of theophylline metabolism in man [Fuhr et al. unpublished observation]. Investigations have now been done in vitro to establish whether verapamil is an inhibitor of and a substrate for CYPIA2. was found, but only 4 data points were available for analysis. The 35% inhibition of caffeine 3-demethylation by verapamil clearly indicates that verapamil binds to CYP1A2, since no other isoenzyme is expected to contribute significantly to the 3-demethylation of caffeine under t- 100- o o_ c~ 80- ¢. 60- 40- Verapamil as an inhibitor of CYP1A2

Journal

European Journal of Clinical PharmacologySpringer Journals

Published: Apr 1, 1992

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