Tianeptine and its main metabolite pharmacokinetics in chronic alcoholism and cirrhosis.
The effect of chronic alcoholism (with or without associated moderate cirrhosis) on the disposition of the antidepressant tianeptine, which is devoid of substantial first-pass metabolism, was examined in 21 patients and 11 age-matched controls. Pharmacokinetic parameters for tianeptine and its C5 acid analogue metabolite (MC5 metabolite) were estimated by non-compartmental analysis. The area under the curve (AUC) for tianeptine, following a 12.5mg single oral dose, was decreased by 31% in chronic alcoholics and increased by only 14% in cirrhotics, compared to controls. These changes did not attain statistical significance. The trend of changes in the AUC for the MC5 metabolite was similar to that observed for the parent drug. No statistical difference was found in the terminal half-life for both tianeptine and its MC5 metabolite between patients and controls. On the basis of this study, it appears unnecessary to modify the proposed dosage regimen used in clinical trials (tianeptine sodium salt 12.5mg 3 times daily) in chronic alcoholics with or without associated moderate cirrhosis.
Royer
R J
RJ
Service de Pharmacologie Clinique et Toxicologie, Hôpital Central, Nancy, France.
Royer-Morrot
M J
MJ
Paille
F
F
Barrucand
D
D
Schmitt
J
J
Defrance
R
R
Salvadori
C
C
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D013841:Thiazepines / Q000097:blood / Q000493:pharmacokinetics*
D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine