Pharmacokinetics of Ketamine and Norketamine After Oral Administration of a Liquid Formulation of Ketamine

Abstract

Background: Ketamine and its active metabolite, norketamine, have analgesic actions. A liquid formulation of ketamine has been prepared in some hospital pharmacies. The pharmacokinetic parameters of ketamine and norketamine after oral administration have not yet been reported. The objective of this study was to evaluate the pharmacokinetics of oral liquid ketamine in healthy volunteers.

Methods: A liquid formulation of ketamine (1%) was administered to six healthy volunteers at a single oral dose of 5 mL. Venous blood samples (10 mL each) were collected before the administration, and at 0.25, 0.5, 0.75, 1, 1.5, 2, 6, 12 hours after the administration of ketamine. The blood pressure and pulse were measured, and the subjective symptoms were also checked for. The serum concentrations of ketamine and norketamine were measured by the HPLC method.

Results: The Cmax, Tmax and AUC_0-12h of ketamine/norketamine were 29.9 5.3/250.2 28.7 ng/mL, 1.1 0.2/1.6 0.2 h, and 79.0 24.0/1193.1 159.6 nghr/mL, respectively. All of the six subjects reported feeling drunk temporarily around the Tmax of ketamine, and two of the six subjects complained of feeling sleepy around the Tmax of ketamine and norketamine. Furthermore, a significant increase of the mean systolic blood pressure was also noted at 1 and 1.5 hours after administration of ketamine.

Conclusions: Norketamine may contribute to the analgesic effect after oral administration of ketamine. Thus, the liquid formulation of ketamine may be a useful formulation for obtaining effective analgesia.




doi: http://dx.doi.org/10.4021/jcs196e