Effects of nifedipine on hepatic drug oxidation.
To determine whether inhibition of drug oxidation is a general property of all calcium antagonist drugs or just of a few, we measured effects of therapeutic doses of nifedipine on antipyrine biotransformation. Antipyrine was administered in random order to 10 subjects while drug-free and while taking nifedipine 30 mg 3 times daily. Total antipyrine clearance (means +/- SE, 43.1 +/- 4.8 control vs. 50.4 +/- 6.5 ml/min; NS) tended to increase but not significantly. Elimination half-life decreased slightly (13.7 +/- 1.0 control vs. 11.7 +/- 0.9; p less than 0.05). Antipyrine metabolite excretion, measured to evaluate selective oxidative pathways, was unaffected by concurrent nifedipine administration. Nifedipine in therapeutic doses had no effect on antipyrine oxidation, unlike verapamil and diltiazem, both of which inhibit hepatic drug oxidation. Inhibition of drug oxidation appears not to be a general property of calcium antagonist drugs.
Division of Clinical Pharmacology, Brown University, Providence, R.I.
T H
TH
Dickinson
J M
JM
Egan
D R
DR
Abernethy
D000328:Adult; D000983:Antipyrine / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009543:Nifedipine; D000983:Antipyrine