Pharmacokinetics of Lercanidipine in Animals: II. Distribution to and Elimination from Organs and Tissues After Administration of [14C]Lercanidipine to Rats and Dogs. Whole‐Body Autoradiography, Biliary Excretion and Enterohepatic Circulation and Biotransformation in Rats

&NA; [14C]Lercanidipine hydrochloride was administered to rats, p.o. at 3 mg/kg in single and repeated dose, and dogs at 0.5 mg/kg in single dose, to investigate the distribution, biliary excretion, recycling, and elimination of the drug. Radioactivity was rapidly and extensively distributed to organs and tissues in rats and dogs, the levels being higher than in plasma 30 min (rats) and 2 h (dogs) after administration. Decay of radioactivity from the tissues was relatively slower than that in plasma, and the liver appears to be the target organ in both species. After repeated administration to rats, unlike in the single dose study, radioactivity was detectable until 96 h post dose in aorta and cava vein organs, largely investigated in pharmacologic in vitro studies. No difference between radioactivity levels in pigmented and non‐pigmented skin was observed in dogs. Biliary excretion plays an important role in the disposition of lercanidipine in rats and dogs. The radioactivity excreted into the rat bile after single [14C]lercanidipine administration is represented only by metabolites and accounts for 30% of the dose. About 20% of this radioactivity is reabsorbed. Thin‐layer chromatography comparison of the metabolites in bile with reference standards shows that lercanidipine biotransformation involves mainly the oxidation of the dihydropyridine ring and affords to nonactive compounds.