Wittayalertpanya Supeecha, Chompootaweep Sumana, Thaworn Nongnuch
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
J Med Assoc Thai. 2006 Dec;89(12):2116-22.
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.
To conduct a study on the pharmacokinetics of pioglitazone in Thai subjects.
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.
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.
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.
吡格列酮是一种用于治疗2型糖尿病的噻唑烷二酮类化合物，主要通过CYP2C8和CYP3A4代谢。由于CYP2C8存在基因多态性，应考虑种族间药代动力学的变异性。
研究吡格列酮在泰国受试者中的药代动力学。
本研究选取24名泰国健康男性受试者。经过一夜禁食后，每位受试者单次口服30mg吡格列酮片。在给药前及给药后0.5、1、1.5、2、2.5、3、3.5、4、5、6、9、12、24和48小时采集系列血样。用乙腈进行蛋白沉淀后，采用带紫外检测的自动高效液相色谱法（HPLC）测定血浆中的吡格列酮。测定相关药代动力学参数，包括血浆峰浓度（Cmax）、达峰时间（Tmax）、消除速率常数（Kel）、消除半衰期（T1/2）、血浆浓度-时间曲线下面积（AUC(0-t)、AUC(0-inf)）、清除率（Cl）和分布容积（Vd）。
单次口服30mg吡格列酮片后，药物被吸收进入体循环，达峰时间（Tmax）为2.00±1.61（0.5 - 6）小时，血浆水平达到最大浓度（Cmax）为1.14±0.29（0.47 - 1.63）μg/ml。AUC(0-t)和AUC(0-inf)分别为11.47±4.77和16.69±7.75μg·hr/ml。所得吡格列酮的消除速率常数（Kel）为0.08±0.04hr⁻¹，而t1/2为11.19±7.38小时，清除率（Cl）为2.26±1.22L/hr。分布表观容积（Vd）为30.19±13.06L。
对泰国受试者单次口服30mg吡格列酮的药代动力学参数进行了表征。这些参数表明吡格列酮吸收速度快、分布容积小且消除半衰期短。
