Influence of renal failure on cytochrome P450 activity in hypertensive patients using a "cocktail" of antipyrine and nifedipine.

Abstract

OBJECTIVE:

Two substrates were coadministered in a "cocktail" approach to evaluate the contribution of renal failure to drug oxidation.

PATIENTS:

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.

• Authors: V L Lanchote, W C Ping, S R Santos
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 50 Issue 1-2 Pg. 83-9 ( 1996) ISSN: 0031-6970 [Print] Germany
• PMID: 8739816 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antihypertensive Agents
• Drug Combinations
• Cytochrome P-450 Enzyme System
• Nifedipine
• Antipyrine

Topics

• Adult
• Anti-Inflammatory Agents, Non-Steroidal (pharmacokinetics, therapeutic use)
• Antihypertensive Agents (pharmacokinetics, therapeutic use)
• Antipyrine (pharmacokinetics, therapeutic use)
• Biotransformation
• Chromatography, High Pressure Liquid
• Cytochrome P-450 Enzyme System (metabolism)
• Drug Combinations
• Female
• Half-Life
• Humans
• Hypertension (complications, drug therapy, enzymology)
• Kidney Failure, Chronic (complications, enzymology)
• Male
• Middle Aged
• Nifedipine (pharmacokinetics, therapeutic use)