Pharmacokinetics of Oral Rosiglitazone in Taiwanese and Post Hoc Comparisons with Caucasian, Japanese, Korean, and Mainland Chinese Subjects

Kai-Min Chu1, Oliver Yoa-Pu Hu2, Li-Heng Pao3, Cheng-Huei Hsiong3

1Division of Cardiology, Tri-Service General Hospital
2Research and Development, National Defense Medical Center
3Pharmaceutical Research Institute, National Defense Medical Center

Abstract


Purpose. Rosiglitazone, an insulin-sensitizing thiazolidinedione, acts as a ligand for the y-subtype of the peroxisome proliferator-activated receptor in the regulation of glucose homeostasis and lipid metabolism. The aims of this study were to determine the pharmacokinetics of oral rosiglitazone in Taiwanese and to post hoc compare the ethnic differences among Caucasian, Japanese, Korean, and Mainland Chinese. Methods. Twelve Taiwanese healthy male subjects received 4 and 8 mg of rosiglitazone. Similar protocols were used in the previously unpublished studies conducted in 25 Caucasian, 32 Japanese, 8 Korean, and 12 Mainland Chinese healthy male subjects. The 4 mg dose data were used for ethnicity comparisons. Results. The respective pharmacokinetic properties of Taiwanese, Caucasian, Japanese, Korean and Mainland Chinese are: terminal half-life (hr): 4.18 +/- 0.43, 3.96 +/- 1.31, 3.83 +/- 0.78, 4.70 +/- 1.19 and 4.37 +/- 0.63; Cmax (ng/ml): 384.1 +/- 59.3, 260.2 +/- 75.7, 401.9 +/- 102.3, 345.3 +/- 60.6, and 406.2 +/- 52.0; AUC0-inf (h•ng/ml): 2078 +/- 433, 1249 +/- 566, 1901 +/- 397, 1938 +/- 534, and 2158 +/- 498. The Cmax and AUC0-inf of Caucasian were significantly (p = 0.002, 0.008) lower and CL/F and V/F were significantly (p = 0.000, 0.003) higher than those of other races. These differences of Cmax, AUC0-inf, CL/F and V/F between Caucasian and other races became insignificant after normalized by dose and weight. Conclusions. In a given dose by body weight, ethnicity had no significant impact on the pharmacokinetics of rosiglitazone in normal healthy volunteers.

J Pharm Pharm Sci, 10 (4): 411-419, 2007

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