Abstract
The metabolism of DL-verapamil in man was studied after oral administration of an aqueous solution of DL-[14C]verapamil. Between 67 and 71% of the 14C administered was excreted in the urine within 5 days. Verapamil was extensively metabolized; only 3--4% of the dose was excreted in the urine as unchanged drug. Cleavage of the C--N--C bond by N-'dealkylation, preferentially at the C-atom belonging to the shorter side chain, was the main metabolic step. Verapamil and its N-dealkylated metabolites were further metabolized by O-demethylation. Inasmuch as approximately 10 times more of the metabolites formed from the tertiary amine verapamil are secondary amines than are primary amines, it would seem that N-dealkylation of this tertiary amine proceeds at a much higher rate than the N-dealkylation of the secondary amine metabolites to primary amine metabolites.
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|