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  • Title: Disposition of the new antidiabetic agent pioglitazone in rats, dogs, and monkeys.
    Author: Maeshiba Y, Kiyota Y, Yamashita K, Yoshimura Y, Motohashi M, Tanayama S.
    Journal: Arzneimittelforschung; 1997 Jan; 47(1):29-35. PubMed ID: 9037440.
    Abstract:
    The disposition of pioglitazone (CAS 105355-27-9, AD-4833) was studied after oral administration to rats, dogs, and monkeys using 14C-labeled drug. After oral dosing, pioglitazone was well absorbed from the gastrointestinal tract at an extent of 96, 95, and 90% in rats, dogs, and monkeys, respectively. In rats, the concentration of pioglitazone in plasma reached a peak (Cmax 0.71 micrograms/ml) at 4 h (tmax) after dosing and declined with a half-life (t1/2) of 2.6 h. In dogs, tmax, Cmax and t1/2 were 0.5 h 0.32 micrograms/ml and 2.1 h, and those for monkeys were 4.3 h, 0.43 micrograms/ml and 5.3 h, respectively. The drug was metabolized mainly to M-I to M-VI including the pharmacologically active metabolites (M-II, III and IV). The pharmacologically active compounds (total of the unchanged compound and the above three active metabolites) accounted for 87, 71, and 73% of the radioactivity in plasma of rats, dogs and monkeys, respectively. The radioactivity was widely distributed in tissues after oral administration to rats, and decreased to the very low concentration within 24 to 72 h after dosing. Radioactivity dose was almost completely excreted in urine and feces.
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