Background: Pioglitazone is a thiazolidinedione compound used in the treatment of type 2 diabetes, metabolized mainly by CYP2C8 and CYP3A4. Due to genetic polymorphisms in CYP2C8, interethnic variability in pharmacokinetics should be considered.

Objective: To conduct a study on the pharmacokinetics of pioglitazone in Thai subjects.

Material and Method: The present study was performed in 24 Thai male healthy subjects. After an overnight fasting, each subject had a single oral dose of 30 mg pioglitazone tablet. Serial blood samples were collected before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 24 and 48 hours after drug administration. Plasma pioglitazone was determined by automated High Performance Liquid Chromatography (HPLC) with UV detection after deproteinized with acetonitrile. The relevant pharmacokinetic parameters including peak plasma concentration (C_max), time to peak plasma concentration (T_max), elimination rate constant (Kel), elimination half-life (T_1/2), area under the plasma concentration-time curve (AUC_(0-t), AUC_(0-inf)), clearance (Cl) and volume of distribution (Vd) were determined.

Results: After a single oral dose of 30 mg pioglitazone tablet, the drug was absorbed into systemic circulation with time to maximum concentration (T_max) at 2.00±1.61 (0.5-6) hr, and the plasma level reached the maximum concentration (C_max) of 1.14±0.29 (0.47-1.63) μg/ml. The AUC was 11.47±4.77 and 16.69±7.75 μg.hr/ml for AUC_0-t and AUC_0-inf, respectively. The elimination rate constant (Kel) of pioglitazone obtained was 0.08±0.04 hr^-1, whereas the t_1/2 was 11.19±7.38 hrs with the clearance (Cl) of 2.26±1.22 L/hr. The apparent volume of distribution (Vd) was found to be 30.19±13.06 L.

Conclusion: Pharmacokinetic parameters of 30 mg single oral dose of pioglitazone were characterized in Thai subjects. These parameters showed that pioglitazone had a rapid rate of absorption, small volume of distribution and short elimination half-life.

Keywords: Pioglitazone, Pharmacokinetics