Pharmacokinetics of the Antidepressant Tianeptine at Steady State in the Elderly

Abstract

The pharmacokinetics of tianeptine, an antidepressant with an original serotoninergic neurochemical action, was investigated in elderly patients. Kinetic profiles were developed in 12 elderly patients (age range: 72–81 yr) after single (12.5 mg) dose and multiple oral dosages (12.5 mg tid for 17 days). Multiple dosing of tianeptine was well tolerated; no accumulation of the unchanged drug was observed. Tianeptine and its MC₅ metabolite (C₅ acid analogue of tianeptine) reached maximum plasma levels after 1.81 ± .99 and 2.96 ± 1.44 hr, respectively, with values of 353 ± 198 and 81 ± 20 ng/mL, respectively, after a single dose and of 405 ± 202 and 175 ± 85 ng/mL, respectively, after multiple dosing. Minimum plasma concentrations of tianeptine were about half those of its MC₅ metabolite (68 ± 41 and 121 ± 64 ng/mL⁻¹ on day 5), and for each compound, they were not statistically different from day 5 to day 18 of the chronic administration. This finding is compatible with the terminal half‐lives that were observed after the single dose that was 2.8 ± .9 hr for tianeptine and 12.3 ± 7 hr for the MC₅ metabolite. For both compounds, the area‐under‐the‐plasma levels time curve at steady state was as predicted from the initial single dose that showed no deviation from linearity with time. The kinetics of tianeptine in elderly patients were similar to those reported for young adults. However, MC₅ metabolite plasma levels were higher in elderly patients than in younger patients. This observation has led to a recommendation to start the prescription with a reduced daily dose of tianeptine in elderly patients aged 70 years or older and to prescribe 12.5 mg twice daily.