Pharmacokinetics of pioglitazone, a thiazolidinedione derivative, in male Naeini (Iranian fat-tailed) sheep

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Sayed Mehdi Ghoreishi, H. Rajaian, Majid Sheykhzade, M. Alikhani, H. R. Rahmani, A. R. Hajipour , M. Khorvash, H.R. Khodaei

Pioglitazone (PGT) belongs to thiazolidinedione (TZD) family or insulin sensitizers that are potent ligands for peroxisome proliferator activated receptor gamma and are used in the treatment of type 2 diabetes mellitus. It has been shown that injection of TZD in cattle has some useful effects on blood parameters but there is no published study with respect to the feeding of TZDs in ruminants till now. Therefore, the aim of this study was to determine the bioavailability and several other pharmacokinetic parameters of PGT in sheep. A single intravenous (IV) or oral dose of PGT (10 mg/kg) was administered to five male sheep. Blood samples were collected at various time intervals, and PGT concentration was measured by a validated high-performance liquid chromatography method. The data obtained were best fitted into a two-compartment model for the IV route, and non-compartmental approach for oral route. The bioavailability of PGT was obtained to be approximately 62%. After IV injection of PGT, the elimination half-life (t 1/2ß), the volume of distribution at steady-state (V ss) and the elimination rate constant (k el) were obtained to be 4.04±0.88 h, 0.30±0.06 L/kg and 0.47±0.09 h-1, respectively. After oral administration of PGT, highest drug concentration observed in plasma (C max), the time (t max) at which C max occurs, half-life (t 1/2), absorption rate constant (k ab) and elimination rate constant (k el) were obtained to be 10.2±1.3 µg/mL, 6.4±0.3 h, 4.42±0.21 h, 0.16±0.01 h-1 and 0.16±0.01 h-1, respectively.
Original languageEnglish
JournalJournal of Applied Animal Research
Volume40
Issue number3
Pages (from-to)208-214
Number of pages7
ISSN0971-2119
DOIs
Publication statusPublished - Sep 2012

ID: 38157995