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 in
increasing insulin sensitivity and in the treatment of type 2 diabetes mellitus in humans. Pioglitazone has
been proposed as a potential feed additive to reduce insulin resistance and consequently some of the
metabolic disorders in transition cows. This study was aimed at determining the pharmacokinetic
parameters of pioglitazone following oral administration (PO) or intravenous (IV) injection. Six lactating
Holstein cows were randomly assigned into two groups (n=3 cows per group) in a crossover design, and
administered with pioglitazone (8 mg/kg BW) either per-oral (PO) or intravenously (IV), with an 8-day
washout period. Blood samples were collected from the jugular vein before and up to 48 h after pioglitazone
administration. Plasma pioglitazone concentration was determined by HPLC. The data were analyzed using
a non-compartmental model for PO route, and a two-compartmental model for the IV route. The
bioavailability of PO-administered pioglitazone was 58% and the highest plasma concentration (Cmax), the
time (tmax) at which the drug reached Cmax, half-life (t1/2), absorption rate constant (kab) and elimination rate
constant (kel) were 11.57±1.44 μg/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 (t1/2β), volume distribution (Vss) and elimination rate constant (kel) after IV
injection were 5.10±0.62 h, 0.12±0.01 L/kg and 0.47±0.06 h-1, respectively. Because of the relatively high
bioavailability and half-life, pioglitazone may be useful for oral administration as an insulin-sensitizing
agent in dairy cows.