Kinetics of propiverine as assessed by radioreceptor assay in poor and extensive metabolizers of debrisoquine

Eur J Drug Metab Pharmacokinet. 1993 Jul-Sep;18(3):265-72. doi: 10.1007/BF03188807.

Abstract

A pharmacokinetic study with 30 mg propiverine p.o. was performed in healthy volunteers (10 males, 6 females, age 36-56 years, body weight 55-100 kg, body height 162-184 cm, Broca index 0.96-1.19). 8 of them were poor and 8 extensive metabolizers of the debrisoquine type hydroxylation polymorphism. The total anticholinergic activity of the parent compound and active metabolites was measured with a radioreceptor assay calibrated with the metabolite M2. The affinity of this metabolite to the muscarinic receptors was similar to that of atropine. The urinary excretion of 3 major metabolites was determined with TLC and densitometry. Arterial blood pressure, heart rate, diameter of pupils, accommodation and parotic salivary flow were also measured. The concentrations of anticholinergic equivalents of propiverine were below 1 ng/ml of M2. 1.4-6.0% of the dose were excreted as N-oxidized metabolites into the urine. The poor and extensive metabolizers of debrisoquine did not differ significantly with regard to the concentration time behaviour of the active drug components, pattern of major metabolites, adverse drug reactions or any pharmacodynamic parameters measured.

MeSH terms

  • Adult
  • Benzilates / administration & dosage
  • Benzilates / pharmacokinetics*
  • Benzilates / urine
  • Biotransformation
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / drug effects
  • Debrisoquin / metabolism*
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hydroxylation
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / drug effects
  • Parasympatholytics / administration & dosage
  • Parasympatholytics / pharmacokinetics*
  • Parasympatholytics / urine
  • Polymorphism, Genetic
  • Radioligand Assay
  • Receptors, Muscarinic / metabolism

Substances

  • Benzilates
  • Parasympatholytics
  • Receptors, Muscarinic
  • propiverine
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6
  • Debrisoquin