Bioequivalence Study of Duloxetine Hydrochloride 60 Mg Ec Capsules in the Fasting and Fed States in Healthy Thai Male Volunteers

Abstract

Duloxetine is one of the serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors (SNRIs). Because it is used extensively in both psychiatric and non-psychiatric conditions, a generic product of duloxetine hydrochloridehas been developed with lower price by the Government Pharmaceutical Organization (GPO) which would be benefit for patients. A randomized, open label, two-treatment, two-period, two-sequence, single dose, crossover, bioequivalence study of generic duloxetine 60 mg EC capsules of GPO, Thailand, and the reference product, Cymbalta^®EC capsules, of Lilly S.A., Spain, in healthy human male adult subjects, under fasting and fed conditions was carried out. Washout period was 10 days between treatments. Blood samples were collected at predefined time points up to 72 hours. Plasma concentrations of duloxetine were analyzed using liquid chromatography tandem mass spectrometry. A non-compartmental model was used for pharmacokinetic analysis. The 90% CI for the ratios of mean AUC_0-tlast, AUC_0-∞ and C_max for the test/reference in the fasting condition were 102.3 (95.27-109.95), 102.5 (95.27-110.26) and 99.3 (92.69-106.32), respectively. In the fed condition, the 90% CI for the ratios of mean AUC_0-tlast, AUC_0-∞ and C_max for the test/reference were 98.9 (92.08-106.28), 98.8 (91.80-106.39) and 92.7 (85.18-100.90), respectively. These values were within the acceptable range of 80.00-125.00. Both the formulations were well tolerated. No clinically significant or serious adverse drug reactions were observed. Therefore, two formulations of duloxetine, Duloxetine GPO 60 mg EC capsules and Cymbalta^®, were bioequivalent and can probably be used interchangeably.