Pharmacokinetic and bioequivalence study of an oral 8 mg dose of rosiglitazone tablets in Thai healthy volunteers.
BACKGROUND
Rosiglitazone maleate is an antihyperglycemic agent in the thiazolidinedione class. It is indicated for the treatment of patients with type 2 diabetes mellitus. A new product of rosiglitazone has been developed. The pharmacokinetic in Thai subjects should be considered and the bioequivalent data of new generic product is required in order to assure the quality and performance.


OBJECTIVE
To characterize the pharmacokinetics of rosiglitazone in Thai subjects and compare the bioequivalence of generic product of a single oral 8 mg rosiglitazone tablet with the innovator's product.


METHODS
The present study was performed in 24 healthy Thai male volunteers. Each received a single oral dose of 8 mg rosiglitazone tablet. Double blind randomized two-way crossover design was used with two weeks washout period between treatments. After drug administration, a serial blood sample was collected over a period of 48 hours. Rosiglitazone plasma level was determined by HPLC with fluorescence detector. The pharmacokinetic parameters were determined by non compartment model. For bioequivalence determination, the difference of Cmax, AUC(0-t) and AUC(0-inf) were analyzed by ANOVA and 90% confidence interval.


RESULTS
The mean +/- SD of pharmacokinetic parameters of generic product and the innovator's product were 0.82 +/- 0.52 vs. 1.02 +/- 1.50 hr of Tmax, 796.51 +/- 155.19 vs. 723.48 +/- 134.69 ng/ml of Cmax, 3.94 +/- 0.80 vs. 3.87 +/- 0.77 hr of T1/2, 4,308.43 +/- 1,006.28 vs. 4,135.66 +/- 1,061.96 ng x hr/ml of AUC(0-t), 4,384.65 +/- 1,035.15 vs. 4,183.87 +/- 1,075.39 ng x hr/ml of AUC(0-inf), respectively. The 90% confidence interval of mean difference of Cmax, AUC(0-t) and AUC(0-inf) (log transformed data) of generic product compared to the innovator's product were 98.42-122.18%, 97.28-109.66% and 97.79-110.30%, respectively. They were within the range of the acceptance criteria 80-125%.


CONCLUSIONS
Pharmacokinetic parameters of a single oral dose of 8 mg rosiglitazone tablet were characterized in Thai healthy subjects. These parameters showed that rosiglitazone was rapidly absorbed with a short elimination half-life. The two formulations of rosiglitazone were bioequivalent.
Wittayalertpanya
Supeecha
S
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Chompootaweep
Sumana
S
Thaworn
Nongnuch
N
Khemsri
Wandee
W
Intanil
Nuntana
N
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D044466:Asian People; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005453:Fluorescence; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013607:Tablets; D013785:Thailand; D013810:Therapeutic Equivalency; D045162:Thiazolidinediones / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D055815:Young Adult
D007004:Hypoglycemic Agents; D013607:Tablets; D045162:Thiazolidinediones; D000077154:Rosiglitazone