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The pharmacokinetics of the antidepressant tianeptine and its main metabolite in healthy humans – influence of alcohol co‐administration
Author(s) -
Salvadori C,
Ward C,
Defrance R,
Hopkins R
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb01021.x
Subject(s) - tianeptine , pharmacokinetics , metabolite , volume of distribution , pharmacology , oral administration , chemistry , active metabolite , absorption (acoustics) , half life , antidepressant , medicine , hippocampus , physics , acoustics
Summary— A balanced 3 way cross‐over study involving 12 young healthy volunteers (6 men and 6 women) was used to determine the pharmacokinetic parameters of the antidepressant tianeptine following a single dose administered by oral and intravenous route. The influence of alcohol on the pharmacokinetics of tianeptine when given per os was also investigated. Kinetic parameters of metabolite MC 5 , the C 5 side chain beta–oxidation product of tianeptine, were simultaneously determined. Following intravenous administration total clearance and volume of distribution of tianeptine were 230±59 ml·min −1 and 0.47±0.14 1.kg −1 respectively. When given orally, tianeptine was absorbed rapidly (tmax = 0.94 ± 0.47 h). The mean systemic availability was estimated to be 99 ±29%. Tianeptine was eliminated from plasma with a half‐life of 2.5± 1.1 h, mainly via extrarenal route since its renal clearance averaged 0.38±0.47 ml·min −1 . Plasma levels of metabolite MC 5 were lower than those of the parent drug but decreased with a longer half‐life (7.2 ±5.7 h). Alcohol co‐administration decreased tianeptine absorption rate and lowered tianeptine plasma levels by about 30% but did not affect those of the MC 5 metabolite.