Pharmacokinetics and Bioavailability of Tianeptine in the Elderly

Abstract

A balanced 2-way crossover study involving 12 elderly volunteers was used to determine the pharmacokinetic parameters of the antidepressant tianeptine following a single dose administered by oral and intravenous routes. Pharmacokinetic parameters of metabolite MC5, the C5 side-chain β-oxidation product of tianeptine, were simultaneously determined. Tianeptine was absorbed rapidly [peak concentration (Cmax) = 261 ± 70 µg/L, and time to Cmax (tmax) = 1.59 ± 0.63 hours] and efficiently, with a bioavailability of 84.6 ± 14.0%. After intravenous administration, following limited distribution in the tissues [volume of distribution at steady-state (Vdss) = 0.44 ± 0.08 L/kg] tianeptine was rapidly eliminated from the plasma (t½z = 3.1 ± 1.1 hours) mainly through biotransformation [renal clearance (CLR) < 1 ml/min; total clearance (CLT) = 139 ± 28 ml/min]. The MC5 metabolite appeared 0.18 ± 0.04 hours following the beginning of intravenous administration (tmax 2.96 ± 0.95 hours; Cmax = 83 ± 29 µg/L). MC5 was excreted with a terminal half-life of 11.9 ± 8.0 hours; its renal clearance was low (3.1 ± 2.3 ml/min). After oral administration, the pharmacokinetics of the MC5 metabolite remained unchanged, except for tmax which was delayed (tmax = 3.70 ± 0.61 hours). This study has shown that the bioavailability of tianeptine is high in elderly subjects. Apart from drowsiness observed only following intravenous administration, tianeptine was well tolerated, particularly with regard to cardiovascular effects. © 1990, Adis International Limited. All rights reserved.