The pharmacokinetics of pioglitazone in Thai healthy subjects.
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.


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) microg/ml. The AUC was 11.47 +/- 4.77 and 16.69 +/- 7.75 microg x 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 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.


CONCLUSIONS
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.
Wittayalertpanya
Supeecha
S
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Chompootaweep
Sumana
S
Thaworn
Nongnuch
N
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D000077205:Pioglitazone; D013785:Thailand; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone