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Original Articles

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

, , , , , , & show all
Pages 208-214 | Received 11 Oct 2011, Accepted 02 Dec 2011, Published online: 27 Feb 2012
 

Abstract

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 1/2β), 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.

Acknowledgements

The authors acknowledge SamiSaz Pharmaceutical Co. and Osvah Pharmaceutical Co. as they supplied PGT for the pilot study. Kind helps of the following colleagues with respect to laboratory and field works of this study is greatly appreciated: H.R. Khoshooee, A. Nowrouzi, E. Ghasemi, S.M. Nasrollahi, A. Shahmoradi, H. Beyranvand, A.A. Hajialiakbari, A. Rahmanian and J. Razavi. This research was financially supported by Isfahan University of Technology.

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