Plasma pharmacokinetics of pioglitazone following oral or intravenous administration in Holstein cows

Pioglitazone belongs to the thiazolidinedione (tzd) class of antidiabetic agents, with proven efficacy inincreasing insulin sensitivity and in the treatment of type 2 diabetes mellitus in humans. pioglitazone hasbeen proposed as a potential feed additive to reduce insulin resistance and consequently some of themetabolic disorders in transition cows. this study was aimed at determining the pharmacokineticparameters of pioglitazone following oral administration (po) or intravenous (iv) injection. six lactatingholstein cows were randomly assigned into two groups (n=3 cows per group) in a crossover design, andadministered with pioglitazone (8 mg/kg bw) either per-oral (po) or intravenously (iv), with an 8-daywashout period. blood samples were collected from the jugular vein before and up to 48 h after pioglitazoneadministration. plasma pioglitazone concentration was determined by hplc. the data were analyzed usinga non-compartmental model for po route, and a two-compartmental model for the iv route. thebioavailability of po-administered pioglitazone was 58% and the highest plasma concentration (cmax), thetime (tmax) at which the drug reached cmax, half-life (t1/2), absorption rate constant (kab) and elimination rateconstant (kel) were 11.57±1.44 ?g/ml, 5.67±0.07 h, 7.10±0.32 h, 0.28±0.09 h-1 and 0.10±0.013 h-1,respectively. elimination half-life (t1/2b), volume distribution (vss) and elimination rate constant (kel) after ivinjection were 5.10±0.62 h, 0.12±0.01 l/kg and 0.47±0.06 h-1, respectively. because of the relatively highbioavailability and half-life, pioglitazone may be useful for oral administration as an insulin-sensitizingagent in dairy cows.