Comparative Bioavailability Of Two Sertraline Formulations In Healthy Human Volunteers After A Single Dose Administration [biodisponibilidade Comparativa De Duas Formulações De Sertralina Em Voluntários Humanos Sadios Após A Administração De Uma única Dose]

Objective: To compare the bioavailability of two sertraline tablet (50 mg) formulations (Sertralina from Eurofarma Laboratórios Ltd., Brazil, as test formulation and Zoloft® from Laboratódos Pfizer Ltd., Brazil, as reference formulation) in 24 volunteers of both sexes. Material and methods: The study was conducted open with randomized two-period crossover design and two-weeks washout period. Plasma samples were obtained over a 96-hour interval. Sertraline concentrations were analyzed by combined reversed liquid-phase chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using selected ion monitoring method. From the sertraline plasma concentration vs time curves the following pharmacokinetic parameters were obtained: AUClast, AUC0-∞ and C max. Results: Geometric mean of Sertralina/Zoloft® 50 mg individual percent ratio was 98.9% for AUClast, 99.0% for AUC 0-∞ and 93.7% for Cmax. The 90% confidence intervals were 91.4%-107.0%, 89.7-109.4%, and 84.5%-104.0%, respectively. Conclusion: Since the 90% CI for Cmax, AUClast and AUC0-∞ were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that Sertraline 50 mg tablet by Eurofarma Laboratórios Ltd. was bioequivalent to Zoloft® tablet 50 mg, according to both the rate and extent of absorption.611-28084Eap, C.B., Baumann, P., Analytical methods for the quantitative determination of selective serotonin reuptake inhibitors for therapeutic drug monitoring purposes in patients (1996) J Chromatogr B Biomed Appl, 686, pp. 51-63Eap, C.B., Bouchoux, G., Amey, M., Cochard, N., Savary, L., Baumann, P., Simultaneous determination of human plasma levels of citalopram, paroxetine, sertralina, and their metabolites by gas chromatography-mass spectrometry (1998) J Chromatogr Sci, 36, pp. 365-371Bioavailability and bioequivalence requerimentsabbreviated applicationsproposed revisions - FDA. Proposed rule (1998) Fed Regist, 63, pp. 64222-64228. , Food and Drug AdministrationKim, K.M., Jung, B.H., Choi, M.H., Woo, J.S., Paeng, K.J., Chung, B.C., Rapid and sensitive determination of sertralina in human plasma using gas chromatography-mass spectrometry (2002) J Chromatogr B Analyt Technol Biomed Life Sci, 769, pp. 333-339Koe, B.K., Weissman, A., Welch, W.M., Browne, R.G., Sertralina, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin (1983) J Pharmacol Exp Ther, 226, pp. 686-700Milner, D.A., Hall, M., Davis, G.G., Brissie, R.M., Robinson, C.A., Fatal multiple drug intoxication following acute sertralina use (1998) J Anal Toxicol, 22, pp. 545-548Moraes, M.E., Lerner, F.E., Perozin, M., Moraes, M.O., Frota Bezerra, F.A., Sucupira, M., Corso, G., De Nucci, G., Comparative bioavailability of two sertralina tablet formulations in healthy human volunteers after a single dose administration (1998) Int J Clin Pharmacol Ther, 36, pp. 661-665Sifton, D.W., Physicians' Desk Reference (2001) Medical Economics, Thomson Healthcare, 55th Edition, pp. 2553-255