title: Pharmacokinetics of pioglitazone in lean and obese cats.
abstract: 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.
authors.affiliation: Department of Comparative Biosciences Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Hoenig
authors.forename: D C
authors.initials: DC
authors.lastname: Ferguson
authors.forename: L
authors.initials: L
authors.lastname: Dirikolu
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002371:Cat Diseases / Q000097:blood / Q000378:metabolism*; D002415:Cats; D005260:Female; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000662:veterinary*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone