Pharmacokinetics and metabolism of 14C-glipentide, a new antidiabetic, after oral and intravenous administration.

The pharmacokinetic study of 14C-glipentide in male Wistar rats shows, at 0.2 mg/kg doses, that blood radioactivity drops quickly. The metabolization is effected in the liver and leads to four labelled metabolites which are eliminated mainly by the bile. The physiological disposition of unchanged glipentide can be described by a two-compartment open model. Autoradiography and quantitative studies have shown that the liver presents the highest concentration of radioactivity, that diminishes to a very low value 96 h after the administration. In the other tissues the radioactivity is never large, even following repeated administrations. The plasma protein binding does not change with the time, and it can be presumed that binding forces of glipentide and its metabolites to plasma proteins are similar. Glipentide is very well absorbed. The urinary and fecal elimination of radioactivity is similar after oral and i.v. administration.