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Pharmacokinetics of pioglitazone in lean and obese cats 1
Author(s) -
CLARK M. H.,
HOENIG M.,
FERGUSON D. C.,
DIRIKOLU L.
Publication year - 2012
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2011.01341.x
Subject(s) - pioglitazone , pharmacokinetics , thiazolidinedione , bioavailability , oral administration , cats , medicine , pharmacology , type 2 diabetes , rosiglitazone , insulin , endocrinology , diabetes mellitus , chemistry
Clark, M. H., Hoenig, M., Ferguson, D. C., Dirikolu, L. Pharmacokinetics of pioglitazone in lean and obese cats. J. vet. Pharmacol. Therap. 35 , 428–436. Pioglitazone is a thiazolidinedione insulin sensitizer that has shown efficacy in Type 2 diabetes and nonalcoholic fatty liver disease in humans. It may be useful for treatment of similar conditions in cats. The purpose of this study was to investigate the pharmacokinetics of pioglitazone in lean and obese cats, to provide a foundation for assessment of its effects on insulin sensitivity and lipid metabolism. Pioglitazone was administered intravenously (median 0.2 mg/kg) or orally (3 mg/kg) to 6 healthy lean (3.96 ± 0.56 kg) and 6 obese (6.43 ± 0.48 kg) cats, in a two by two Latin Square design with a 4‐week washout period. Blood samples were collected over 24 h, and pioglitazone concentrations were measured via a validated high‐performance liquid chromatography assay. Pharmacokinetic parameters were determined using two‐compartmental analysis for IV data and noncompartmental analysis for oral data. After oral administration, mean bioavailability was 55%, t 1/2 was 3.5 h, T max was 3.6 h, C max was 2131 ng/mL, and AUC 0–∞ was 15 556 ng/mL·h. There were no statistically significant differences in pharmacokinetic parameters between lean and obese cats following either oral or intravenous administration. Systemic exposure to pioglitazone in cats after a 3 mg/kg oral dose approximates that observed in humans with therapeutic doses.