Pharmacokinetics and Bioequivalence Study of Escitalopram Oxalate Formulations after Single-dose Administration in Healthy Chinese Male Volunteers

 

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Abstract

The aim of the present study was to compare the bioavailability of escitalopram (CAS 128196-01-0) from two escitalopram oxalate (CAS 219861-08-2) tablets (escitalopram 10 mg tablet as test preparation and 10 mg tablet commercially available original tablet of the drug as reference preparation) in 20 Chinese healthy male volunteers, aged between 19 and 27. The study was conducted according to an open, randomized, single blind, 2-way crossover study design with a wash-out phase of 14 d. Blood samples for pharmacokinetic profiling were taken up to 156 h post-dose, and escitalopram plasma concentrations were determined with a validated liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Maximum plasma concentrations (C_max) of 9.85 ± 1.79 ng/ml (test) and 9.92±2.14ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC_0–∞) of 428.40 ± 140.25 ng · h/ml (test) and 413.73 ± 144.81 ng · h/ml (reference), AUC_0–t of 401.33 ± 120.61 ng · h/ml (test), 385.42 ± 117.73 ng · h/ml (reference) were calculated. The median T_max was 4.3 ± 1.8h, 4.1 ± 1.5 h for test and reference formulation, respectively. Plasma elimination half-lives (t_1/2) of 36.30 ± 8.93 h (test), 36.70 ± 9.99 h (reference) were determined. Both primary target parameters, AUC_0–∞ and AUC_0–t were tested parametrically by analysis of variance (ANOVA) and relative bioavailabilities were 105.1 ± 10.8% for AUC_0–∞, 104.9 ± 11.1% for AUC_0–t. Bioequivalence between test and reference preparation was demonstrated for both parameters, AUC_0–∞ and AUC_0–t. The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%–125%. That means that the test formulation is bioequivalent to the reference formulation for escitalopram.

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