Influence of renal failure on cytochrome P450 activity in hypertensive patients using a "cocktail" of antipyrine and nifedipine.
OBJECTIVE
Two substrates were coadministered in a "cocktail" approach to evaluate the contribution of renal failure to drug oxidation.


METHODS
Nineteen hypertensive patients, nine of them with chronic renal failure (CLCR 38.9 vs 102.3 ml.min-1 1.73 m-2), were investigated after peroral administration of a combination of antipyrine (500 mg, in capsules) and nifedipine (10 mg, in Oxcord capsules) in the morning after an overnight fast.


RESULTS
This "cocktail" approach made it possible to characterize in vivo the activities of different forms of cytochrome P450 in a single-study protocol using the total clearance of nifedipine and clearance for production of 3-hydroxymethylantipyrine (HMA), 4-hydroxyantipyrine (OHA) and norantipyrine (NORA). With this "cocktail" approach (antipyrine plus nifedipine), we can suggest a selective effect on the activities of cytochrome P450 forms associated with the formation of dehydronifedipine (P450 III A4) and of NORA in patients with mild renal failure under long-term antihypertensive therapy.
Lanchote
V L
VL
Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
Ping
W C
WC
Santos
S R
SR
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000983:Antipyrine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D004338:Drug Combinations; D003577:Cytochrome P-450 Enzyme System; D009543:Nifedipine; D000983:Antipyrine