Plasma levels and urinary excretion of verapamil, norverapamil, N-dealkylverapamil (D617), N-dealkylnorverapamil (D620) following oral administration of a slow-release preparation

Int J Clin Pharmacol Res. 1985;5(2):99-107.

Abstract

The kinetics of verapamil and of its N-dealkylated metabolites (norverapamil, D617, D620) were studied in six cardiac patients with normal cardiac indexes after 120 mg oral administration of the drug both as conventional preparation and as slow-release preparation. Following a dose of the slow-release preparation, the drug concentration curves were smoother and the mean bioavailability was lower in comparison with the conventional preparation. A patient taking inducing agents (phenobarbital and phenytoin) exhibited a strikingly low bioavailability. Following administration of the conventional preparation, the mean plasma half-lives of verapamil, norverapamil, D617 and D620 were 4.4, 6.6, 8.5, and 15.8 h respectively and the drug concentrations showed a triexponential decay. Urinary excretion data indicate that a saturation phenomenon may occur at level of renal tubular transport and that a competition may be suspected between D620 and the other compounds. It is concluded that various mechanisms, i.e. changes in hepatic and renal clearances, occurrence of a deep compartment, and the properties of the pharmaceutical preparation may affect verapamil kinetics during long-term treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiac Catheterization
  • Delayed-Action Preparations
  • Female
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Nitriles*
  • Plasma / analysis
  • Verapamil / administration & dosage
  • Verapamil / analogs & derivatives*
  • Verapamil / blood
  • Verapamil / metabolism*
  • Verapamil / urine

Substances

  • Delayed-Action Preparations
  • Nitriles
  • alpha-(3-aminopropyl)-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile
  • 2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile
  • norverapamil
  • Verapamil