Screening for cytochrome P450 3A in man: studies with midazolam and nifedipine.
This report describes work directed towards the development of a screening technique for cytochrome P450 3A activity which should be valid for a variety of drugs metabolized by this enzyme. A significant correlation (P < 0.01) was found between the ratio of the plasma concentration of nifedipine to that of its oxidized metabolite and the area under the time curve for the plasma concentration of midazolam. It is suggested that the nifedipine: metabolite ratio might have general predictive value for the metabolism of orally administered cytochrome P450 3A substrates.
Yeates
R A
RA
Department of Pharmacology, Pfizer Germany Research and Development, Illertissen, Germany.
Scharpf
F
F
Laufen
H
H
Zimmermann
T
T
D000328:Adult; D019540:Area Under Curve; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics; D002849:Chromatography, Gas; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D005260:Female; D018757:GABA Modulators / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D018757:GABA Modulators; D019392:Cytochrome P-450 CYP2E1; D009543:Nifedipine; D008874:Midazolam