Studies on the Metabolic Fate of Loprinone Hydrochloride (1): Blood Level, Distribution, Metabolism, Excretion after a Single Intravenous Administration to Rats

Abstract

The pharmacokinetics of Loprinone hydrochloride, a new cardiotonic agent, was investigated after a single intravenous administration of ¹⁴C-labelled compound to male rats.
1. After a single intravenous administration of ¹⁴C-Loprinone hydrochloride to rats, the plasma level of radioactivity rapidly decreased biexponentially, with the corresponding half-lives of 9.7 min and 3.6 hr.
2. Radioactivity was distributed rapidly in all tissues. A high level of radioactivity was observed in the liver and kidney, followed by the duodenum. The tissue levels of radioactivity decreased with half-lives similar to that in blood. Similar distribution profiles were observed with whole body autoradiography, and at 96 hr after dosing, the level of radioactivity in all tissues was very low reaching the detection limit.
3. Loprinone hydrochloride was hardly metabolized. In the urine and feces, the unchanged form was mainly found, however, small amount of metabolites, amine form and enol-O glucuronide of unchanged form, were also detected.
4. Biliary excretion of radioactivity was 46.3% of dose within 24 hr after dosing.
5. Within 24 hr after dosing, the excretion of radioactivity was 43.0 and 47.2% of dose in urine and feces, respectively, and the total excretion of radioactivity was 97.2% of dose within 96 hr.