The Pharmacokinetics of Pioglitazone in Thai Healthy Subjects
Supeecha Wittayalertpanya MSc*, Sumana Chompootaweep MD, MPH*, Nongnuch Thaworn MSc*
Affiliation : * Department of Pharmacology, Faculty of Medicine, Chulalongkorn University
Background : Pioglitazone is a thiazolidinedione compound used in the treatment of type 2 diabetes, metabo-
lized 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.
Materials and Methods : 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 (Cmax), time to peak plasma concentration (Tmax), elimination rate constant (Kel),
elimination half-life (T1/2), 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 (Tmax) at 2.00 + 1.61 (0.5-6) hr, and the plasma level reached the
maximum concentration (Cmax) 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 AUC0-t and AUC0-inf, respectively. The elimination rate constant (Kel) of pioglitazone obtained
was 0.08 + 0.04 hr-1, whereas the t1/2 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
