The effect of intravenous tianeptine on an established model of opioid-induced respiratory depression (OIRD) in healthy volunteers: a population pharmacokinetic and pharmacodynamic study

Rationale
The use of opioids comes with serious side effects of which opioid-induced respiratory depression (OIRD) is most dangerous. The use of drugs that antagonize OIRD but simultaneously do not affect (or even advance) analgesia would be a significant improvement over current OIRD treatment options. A possible novel option for respiratory stimulation could be with administration tianeptine. Tianeptine is an atypical antidepressant and cognitive enhancer medicine that can be administered orally or intravenously. It induces neuroplastic changes and modulates noradrenergic, dopaminergic and glutamatergic pathways. In the current experimental pharmacokinetic-pharmacodynamics modeling study we will investigate the effect of intravenous tianeptine. The study will have two parts. In part 1 we will study the pharmacokinetics (PK) of intravenous tianeptine in 6 healthy volunteers. In part 2 we will perform a pharmacokinetic-pharmacodynamic modeling study to assess the ability of intravenous tianeptine to reverse OIRD induced by administration of the opioid remifentanil (using a double blind randomized placebo-controlled design, tianeptine:placebo = 1:1).

Proof of concept: to study the effect of tianeptine on opioid-induced respiratory depression in healthy volunteers.

In part 1, all blood samples will be taken within 90 minutes following the start of infusion.
In part 2, continuous ventilatory measurements will be collected.

In part 1 we will study the pharmacokinetics (PK) of intravenous tianeptine in 6 healthy volunteers. In part 2 we will perform a pharmacokinetic-pharmacodynamic modeling study to assess the ability of intravenous tianeptine to reverse OIRD induced by administration of the opioid remifentanil (using a double blind randomized placebo-controlled design, tianeptine:placebo = 1:1).