title: Pharmacokinetic and bioequivalence assessment of two formulations of tianeptine sodium in healthy male volunteers.
abstract: BACKGROUND
  Tianeptine is widely used for controlling depressive symptoms.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the bioequivalence between the generic (test) formulation containing tianeptine sodium 12.5 mg and the branded (reference) formulation Stablon® with regard to their pharmacokinetic profiles.
  
  
  METHODS
  A randomized, two-sequence, two-treatment crossover study was conducted in healthy male Korean volunteers. All of the enrolled subjects were allocated to one of two sequence groups. They were administered a tablet of the test or reference formulation and then administered the alternative formulation after a 7-day washout period. The blood samples were taken before dosing and at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, and 10 hours after dosing. The plasma concentrations of tianeptine were analyzed using high-performance liquid chromatography with tandem mass spectrometer. Tolerability was assessed throughout the study.
  
  
  RESULTS
  The pharmacokinetic parameters were assessed in the 40 subjects who completed the study. The tianeptine C(max) for the test formulation was 283.13 ± 57.58 ng/mL (mean ± SD) and that for the reference formulation was 272.50 ± 59.00 ng/mL. The AUC(last) of tianeptine was 803.24 ± 180.94 ng×h/mL for the test formulation and 792.27 ± 180.93 ng×h/mL for the reference formulation. The geometric mean ratio (%) of the test to reference formulation was 104.04 (90% CI, 99.66 - 108.61) for C(max) and 101.30 (98.01 - 104.71) for AUC(last). Clinically significant adverse events were not reported during the study.
  
  
  CONCLUSIONS
  The test and reference formulations of tianeptine were bioequivalent with regard to the pharmacokinetic parameters of Cmax and AUC(last). Both formulations were tolerated by all of the participants.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, and East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Renhua
authors.initials: R
authors.lastname: Zheng
authors.forename: Bo-Hyung
authors.initials: BH
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D056910:Republic of Korea; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D013841:Thiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D016568:Drugs, Generic; D013607:Tablets; D013841:Thiazepines; C050504:tianeptine