The absolute bioavailability of racemic ketamine from a novel sublingual formulation

Abstract

Aim: The principal study objective was to investigate the pharmacokinetic characteristics of a new sublingual ketamine wafer and to establish its absolute bioavailability and local tolerability.

Methods: The study was of open label, two way randomized crossover design in eight healthy male volunteers. Each participant received either a single 10 mg intravenous dose as a constant rate 30 min infusion or a 25mg sublingual dose of ketamine wafer in two treatment periods with a 7 day wash out. Pharmacokinetic blood sampling and local tolerability and safety assessments were carried out during 24 h following both dosing occasions. Plasma concentrations were analyzed by non-compartmental methods and local tolerability was assessed using modified Likert scales.

Results: The median (90% CI lower, upper limit) absolute bioavailability of sublingual ketamine was 29% (27, 31%). The first quantifiable plasma ketamine concentration was observed within 5 min for all eight participants for both routes of administration and the median (min–max) time of the peak plasma concentration was 0.75 h (0.25–1.0 h) after sublingual administration. The ketamine wafer had very good local tolerability.

Conclusion: Sublingual administration of the ketamine wafer resulted in rapid absorption. The ketamine wafer has comparable bioavailability with other oral transmucosal formulations of ketamine but with markedly reduced inter-subject variability, warranting further evaluation as an analgesic adjunct.

Figure 1

Individual racemic ketamine plasma concentration–time curves and geometric mean (bold line) during the first 12 h following a 10 mg dose given during a 30 min i.v. infusion to eight healthy volunteers

Figure 2

Individual racemic ketamine plasma concentration–time profiles and geometric mean (bold line) during the first 12 h following a 25 mg sublingual dose to eight healthy volunteers

Figure 3

Geometric mean racemic ketamine plasma concentration–time profiles during the first 6 h following sublingual administration of 25 mg (continuous line) and 10 mg as a 30 min i.v. infusion (dashed line) to eight healthy volunteers