DISPOSITION OF THE NEW ANTIDIABETIC AGENT PIOGLITAZONE IN RATS, DOGS,AND MONKEYS

The disposition of pioglitazone (CAS 105355-27-9, AD-4833) was studied after oral administration to rats, dogs, and monkeys using C-14-label ed drug. After oral dosing, pioglitazone was well absorbed from the ga strointestinal tract at an extent of 96, 95, and 90 % in rats, dogs, a nd monkeys, respectively. In rats, the concentration of pioglitazone i n plasma reached a peak (C-max 0.71 mu g/ml) al 4 h (t(max)) after dos ing and declined with a half-life (t(1/2)) of 2.6 h. In dogs, t(max), C-max and t(1/2) were 0.5 h, 0.32 mu g/ml and 2.1 h, and those for mon keys were 4.3 h, 0.48 mu g/ml and 5.3 h, respectively. The drug was me tabolized mainly to M-I to M-VI including the pharmacologically active metabolites (M-II, III, and IV). The pharmacologically active compoun ds (total of the unchanged compound and the above three active metabol ites) accounted for 87, 71 and 73 % of the radioactivity in plasma of rats, dogs, and monkeys, respectively. The radioactivity was widely di stributed in tissues after oral administration to rats, and decreased to the very low concentration within 24 to 72 h after dosing. Radioact ivity dose was almost completely excreted in urine and feces.