Serotonin reuptake inhibitors: bioequivalence of sertraline capsules.
The study was designed to evaluate the bioavailability of two sertraline (CAS 79617-96-2) formulations. A bioequivalence study was carried out in 24 healthy male volunteers, who were administered 50 mg capsules of the test formulation (Seralin) and the originator product (reference) as a single dose. The trial was performed according to an open, randomized, cross-over design with a washout period of 14-20 days in one study center. Blood samples were taken up to 96 h post dose, the plasma was separated and the concentrations of sertraline were determined by HPLC-MS-MS. The mean Cmax were 9.01 +/- 2.26 ng/mL and 8.24 +/- 2.14 ng/mL, while the mean AUC0-t were 259.09 +/- 105.36 ng x h/mL and 234.36 +/- 95.18 ng x h/mL for the test and reference formulations, respectively. The mean AUC0-inf were 292.66 +/- 128.09 ng x h/mL (test) and 267.23 +/- 116.40 ng x h/ mL (reference). The mean tmax was 5.88 +/- 1.03 h for the test capsules and 6.17 +/- 1.66 h for the reference formula. The mean t1/2el was 26.49 +/- 6.45 h for the test formulation and 26.23 +/- 6.64 h for the reference formulation. Mean MRT values for the test and reference formulations were 28.14 +/- 5.37 h and 27.81 +/- 5.13 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence interval for the primary target parameters, intra-individual ratios of AUC0-t and Cmax of sertraline were between 1.03 and 1.19 (AUC0-t) as well as between 1.02 and 1.17 (Cmax) and thus within the acceptance ranges for bioequivalence trials. Concerning the secondary parameter tmax the 90% confidence interval for the intra-individual differences was between -1.00 and 0.50 h. In the light of the present study it can be concluded that sertraline test capsules are bioequivalent to the reference formulation.
Koytchev
Rossen
R
Cooperative Clinical Drug Research and Development, Neuenhagen, Germany. mail@ccdrdag.com
Ozalp
Yildiz
Y
Erenmemisoglu
Aydin
A
van der Meer
Mike John
MJ
Alpan
Recep Serdar
RS
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D020280:Sertraline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D002214:Capsules; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline