Tianeptine and its main metabolite. Disposition
in chronic renal failure and haemodialysis

by
Salvadori C, Merdjan H, Brouard R, Baumelou A, Nicot G, Fries D.
Institut de Recherches Internationales Servier,
Courbevoie, Paris, France.
Fundam Clin Pharmacol. 1990;4(6):663-71.


ABSTRACT

The disposition of the antidepressant tianeptine and its MC5 metabolite (pentanoic acid analogue of tianeptine) was studied following a single 12.5 mg oral dose of tianeptine sodium salt in 20 patients with chronic renal failure. In 12 patients (group I) having a creatinine clearance of less than 19 ml.min-1 the pharmacokinetics parameters for tianeptine and MC5 metabolite were determined and compared with those obtained in a matched control group (group II). The other 8 patients (group III) were functionally anephric and were studied during 1 dialysis to assess the haemodialysis clearances of tianeptine and MC5 metabolite. The comparison between groups I and II showed that renal failure did not appear to affect the disposition of parent tianeptine. However, the MC5 metabolite terminal half-life was found to be increased in renal patients compared to controls (14.2 +/- 9.3 h vs 4.9 +/- 1.7 h). Due to a large interindividual variability the difference did not reach a significant level (P = 0.054). According to the antidepressant activity of the MC5 metabolite in pharmacological tests, the sustained rise in its plasma level suggests that a reduced daily dose should be administered and 12.5 mg of tianeptine should be given twice daily to patients with chronic renal failure. In patients from group III elimination of the compounds by haemodialysis was found to be low. The dialysis clearances were 3.9 +/- 9.9 ml.min-1 and 19.2 +/- 8.6 ml.min-1 for tianeptine and its MC5 metabolite respectively. This low dialysability has 2 clinical implications. Firstly, patients currently undergoing haemodialysis and treated by tianeptine could be given the drug without taking dialysis into account. Secondly, haemodialysis does not appear to be an effective method for tianeptine elimination in cases of overdosage.


Metabolism
Anxious depression
Tianeptine (Stablon)
Tianeptine: structure
Memory consolidation
Tianeptine and Panic Disorder
Stress, memory and depression
Discriminative stimulus properties
Tianeptine prevents dendritic atrophy
Neurobiology of mood, anxiety and emotion
Glutamate receptor currents in the hippocampus
Major depression and impaired structural plasticity
Synaptic plasticity in tianeptine-treated tree-shrews
Stress-induced hippocampal atrophy and dysfunction
Tianeptine reduces proinflammatory cytokine production


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