Disposition in rats and mice of chloropractolol, a new β-blocking agent

Abstract

1. The disposition of a new β-blocking agent, chloropractolol, labelled with ¹⁴C and with ³H, has been studied in rats and mice.

2. After i.v. administration to the rat (25 mg/kg) of a mixture of [¹⁴C]- and [³H]chloropractolol, urinary and faecal excretion, biliary elimination and tissue distribution were similar for the two labelled species. However, 3% of the dose was recovered as ¹⁴CO₂.

3. Chloropractolol and/or metabolites did not show high cardioselectivity. Uptake by heart of the two labelled species was very close to that found for [¹⁴C]practolol and [¹⁴C]propranolol.

4. Preliminary metabolic studies using h.p.l.c. have shown that in the rat chloropractolol is extensively metabolized, which contrasts with the more limited metabolism of practolol in the same species. Deacetylation is a minor route of metabolism. A structure for the main urinary metabolite is suggested.