PMID: 38084May 1, 1979

The metabolism of DL-[14C]verapamil in man

Drug Metabolism and Disposition : the Biological Fate of Chemicals
M EichelbaumH J Dengler


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.

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