METABOLISM OF DL-VERAPAMIL-C-14 IN MAN

Abstract

The metabolism of [the antiarrhythmic drug] DL-verapamil in man was studied after oral administration of an aqueous solution of DL-[14C]verapamil. Between 67-71% 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.sbd.N.sbd.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. Approximately 10 times more of the metabolites formed from the tertiary amine verapamil are secondary amines than are primary amines. Apparently, N-dealkylation of the tertiary amine proceeds at a higher rate than the N-dealkylation of the secondary amine metabolites to primary amine metabolites.