Assessment of the pharmacokinetics parameters of an innovative easy to use ketamine sublingual gel formulation for psychiatric facilities – ASPIK

In psychiatric indications, ketamine is given through slow intravenous infusion over several hours that requires a dedicated nurse to reconstitute the appropriate individual dosage (usually 0.5-1 mg/kg) and a specific surveillance of blood pressure during the administration. A low-cost alternative galenic formulation are needed to make it more practical and safer to use. Indeed, the s-enantiomer of ketamine, approved in France for pain relief (Eskesia*) and as an add-on treatment for refractory depression or as an acute add-on in case of emergency (Spravato*), are the most useful in specific psychiatric indications, but both face specific dissemination barriers: the current state of psychiatric staff and wards in France, and the cost for their administration and surveillance, especially compared to treatment as usual. And, because of a low oral bioavaibility, ketamine seems ineffective in oral formulations.
The Agence générale des équipements et produits de santé (AGEPS), the Assistance Publique – Hôpitaux de Paris Central Pharmacy, has developed a patent for a buccal gel formulation of s-ketamine, unlocking the biodisponibility problem.
The aim of this project was develop a ketamine sublingual gel and describe its pharmacokinetics / pharmakodynamic properties in order to provide the psychiatric research community with an easy to administer, low-cost, highly innovative ketamine formulation for future studies, with also an expected facilitated dissemination in psychiatric facilities.
The proposed study will include the pharmaceutical development of a ketamine sublingual gel formulation (including stability) and a phase I pharmacokinetics / pharmacodynamic healthy subjects cross over study to compare intravenous, oral and sublingual gel ketamine properties, at a dose of 0.5mg/kg.