Bioequivalence study of a generic quetiapine in healthy male volunteers.
OBJECTIVE
To study the bioequivalence of a generic quetiapine (Quantia 200, manufactured by the Unison Laboratories Co., Ltd., Bangkok, Thailand) and the innovator product (Seroquel, AstraZeneca, Macclesfield, UK).


METHODS
The study was a randomized, 2-way crossover design with a 2-week washout period in 24 healthy Thai male volunteers. After a single 200 mg oral dosing, serial blood samples were collected at appropriate interval up to 48 h. Plasma quetiapine concentrations were determined by high-performance liquid chromatography (HPLC). Pharmacokinetic parameters were estimated using the WinNonlin software with noncompartment model analysis. Comparative bioequivalence between the two formulations was determined by analysis of variance (ANOVA) for 2-way crossover design.


RESULTS
The mean +/- SD of maximum plasma concentration (Cmax), the area under the plasma concentration-time curve from 0 - 48 h (AUC0-48) and the area under the plasma concentration-time curve from 0 to infinity (AUC0-inf) of Quantia 200 vs. Seroquel were 886.60 +/- 356.50 vs. 811.34 +/- 323.37 ng/ml; 3,754.41 +/- 1,453.00 vs. 3,420.00 +/- 1,229.6 ng x h/ml and 4,015.35 +/- 1,528.25 vs. 3,769.45 +/- 1,296.69 ng x h/ml, respectively. Time to reach Cmax (tmax) of Quantia 200 and Seroquel were 1.08 +/- 0.778 and 1.10 +/- 0.79 h, respectively, and thus not significantly different. The 90% confidence interval of the ratios of the logarithmically transformed of Cmax, AUC0-48 and AUC0-inf were 98.21 - 124.37%, 94.43 - 117.03% and 94.77 - 116.61%, respectively, which were within the acceptable range of 80 - 125%. Power of the test for Cmax, AUC0-48 and AUC0-inf was 92.1%, 96.9% and 97.4%, respectively.


CONCLUSIONS
Quantia 200, used in this study, was bioequivalent to Seroquel in terms of both the rate and extent of absorption.
Mahatthanatrakul
W
W
Department of Pharmacology, Prince of Songkla University, Songkhla, Thailand. werawatthana.m@psu.ac.th
Rattana
K
K
Sriwiriyajan
S
S
Wongnawa
M
M
Ridtitid
W
W
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000069348:Quetiapine Fumarate; D012984:Software; D013785:Thailand; D013810:Therapeutic Equivalency
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D016568:Drugs, Generic; D000069348:Quetiapine Fumarate