Comparative bioavailability/ bioequivalence of two different sertraline formulations: a randomised, 2-period x 2-sequence, crossover clinical trial in healthy volunteers.
ABSTRACT An open-label, randomised, crossover single dose study, using 2 periods x 2 sequences, with a minimum washout period of 4 weeks, was conducted in order to assess the comparative bioavailability of two formulations of sertraline hydrochloride (CAS 79617-96-2) 100 mg tablets. Plasma samples were obtained at intake (baseline) and at +1 h, +2 h, +3 h, +4 h, +5 h, +6 h, +7 h, +8 h, +9 h, +12 h, +24 h, +48 h, +72 h and +96 h post administration. Sertraline plasma concentrations were determined by high pressure liquid chromatography with tandem mass detection (HPLC-MS/MS) and the lower limit of quantification was set at 100.15 pg/mL. Pharmacokinetic parameters used for bioequivalence assessment (AUClast, AUCinf and Cmax) were determined by non-compartmental analysis. Classical 90 % confidence intervals (90CI) were calculated for the overall sample, and for males and females separately, and gender effects were investigated using an appropriate model. The results showed that overall classical 90CI were 84.55-100.32 % for Cmax 86.96-98.68 % for AUClast, and 86.79-98.93 for AUCinf, that is, they were all within the predefined ranges for bioequivalence acceptance. Separate gender analysis showed very similar results for males and females when analysed independently, and no gender effects were detected in bioequivalence analysis (p > 0.05). It may be therefore concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.
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ABSTRACT: INTRODUCTION: Sex differences have been identified in antidepressant treatment; however, it remains unclear to what extent pharmacokinetics contributes to these differences. As current antidepressant pharmacotherapy is less than optimal, understanding the role of sex in pharmacokinetics may substantially contribute to a gender-based optimized treatment. AREAS COVERED: An unrestricted PubMed literature search on antidepressant pharmacokinetics and sex was performed. Sex differences in absorption, distribution, metabolism and elimination of antidepressants, as well as the interaction of sex with age, genetic polymorphisms and gonadal hormones are discussed. We also provide an overview of how each antidepressant presents a particular sex-differentiated pharmacokinetic profile. Most antidepressants present to some extent pharmacokinetic sex differences, which often are further accentuated by gonadal hormones. In most cases, women, particularly elderly women, are expected to have higher exposure to antidepressants when dosed in a similar way as men. EXPERT OPINION: Although the available pharmacokinetic evidence indicates that women should receive lower doses of antidepressants and men should receive higher doses, current guidelines do not recommend dose adjustment, because these sex differences are considered to be clinically insignificant. Unless we understand the link between pharmacokinetics and pharmacodynamics of antidepressants, it will be difficult to determine whether sex differences are of clinical importance or not. Thus, further systematic and particularly focused research is needed on sex differences in pharmacokinetics.Expert Opinion on Drug Metabolism & Toxicology 02/2011; 7(2):213-26. · 2.94 Impact Factor
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ABSTRACT: To determine the bioavailability of 50 mg sertraline tablets between the test product (Zotaline, M&H Manufacturing Co., Ltd, Thailand) and the reference product (Zoloft, Pfizer Australia Pty Ltd, Australia). An open-labeled, single dose, 2-treatment, 2-period, 2-sequence, randomized crossover study under fasting conditions with 14 days washout period was conducted in 24 healthy Thai volunteers. Blood samples were collected before dosing and at frequent intervals for up to 96 h post dose. Analysis of sertraline concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Twenty-four volunteers completed both treatment periods. Pharmacokinetic parameters were determined using the non-compartment model. The 90 percent confidence intervals of the geometric mean ratios (test/reference) of C(max) 104.47% (96.64%-112.93%), AUC(0-96) 108.06% (100.71%-115.94%) and AUC(0-infinity) 108.39% (100.93%-116.40%) fell within the equivalence range (80%-125%). There was no significant difference of the T(max) parameter between the two formulations (p > 0.05). No serious adverse events related to the study drugs were found. The two formulations of sertraline tablets were bio-equivalent in Thai healthy volunteers.Journal of the Medical Association of Thailand = Chotmaihet thangphaet 09/2009; 92(9):1229-33.