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

Eur J Clin Pharmacol. 1996;50(1-2):83-9. doi: 10.1007/s002280050073.


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.

Publication types

  • Clinical Trial

MeSH terms

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


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