Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors.
Following oral administration in the fasting healthy subject, the mean maximum concentration of tianeptine is 334 +/- 79 ng/ml. Absorption of tianeptine from the tablet form is rapid and complete. Maximum plasma concentration is obtained by the first hour following administration (0.94 +/- 0.47 h). Absolute bioavailability is 99 +/- 29%. Tianeptine is thus rapidly and completely absorbed in the tablet form and is not subject to first-pass effect. Distribution of tianeptine in the body is characterized by the following: its rapidity, the mean distribution half-life being about 0.7 h; its limited extent, the apparent volume of distribution being about 0.8 L/kg (0.77 +/- 0.31 L/kg); and protein binding, which averages 93.8 +/- 2.4%. Elimination of tianeptine is characterized by a short mean half-life of 2 h 30 min (2.5 +/- 1.1 h) and by renal excretion of 0.4 ml/min (0.4 +/- 0.4 ml/min). Tianeptine is extensively metabolized. Major metabolites are analogs of tianeptine with a C5 and C3 lateral chain and a N-demethylated derivative. Studies have shown negligible influence on pharmacokinetic parameters of chronic alcoholism even in case of hepatic cirrhosis. In renal failure, and in the elderly, studies have revealed a 1-h prolongation of elimination half-life which suggests that the dosage should be limited to two tablets per day in such cases.
Royer
R J
RJ
Hôpital Central, Nancy, France.
Albin
H
H
Barrucand
D
D
Salvadori-Failler
C
C
Kamoun
A
A
D000284:Administration, Oral; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D006207:Half-Life; D006801:Humans; D012307:Risk Factors; D013607:Tablets; D013841:Thiazepines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D000929:Antidepressive Agents, Tricyclic; D013607:Tablets; D013841:Thiazepines; C050504:tianeptine