Plasma levels and urinary excretion of verapamil, norverapamil, N-dealkylverapamil (D617), N-dealkylnorverapamil (D620) following oral administration of a slow-release preparation.
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.
D000328:Adult; D006328:Cardiac Catheterization; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010949:Plasma / Q000032:analysis; D014700:Verapamil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000652:urine
D003692:Delayed-Action Preparations; D009570:Nitriles; C016906:alpha-(3-aminopropyl)-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile; C482241:2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile; C016904:norverapamil; D014700:Verapamil