Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmentographic assay

Abstract

Ketamine and two of its metabolites were determined up to 24 hours by a sensitive and specific gas chromatographic mass fragmentographic (GCMF) assay in the plasma of seven premedicated surgical patients. Each patient received ketamine in a dose between 2.0 and 2.2 mg/kg given intravenously over a 30-second period. Plasma levels of ketamine varied from 9,000 to 25,800 ng/ml 1 minute after injection to approximately 1,000 ng/ml when the patients began to recover consciousness. Within the next 24 hours, the patients had a complex logarithmic decline after injection. The data suggest rather complex pharmacokinetics with multiple compartments. Ketamine metabolites I and II were also found in the plasma over comparable periods of time. Ketamine metabolite I levels ranged from a high of 245 to 668 ng/ml within 30 minutes after ketamine administration to as low as 15 ng/ml 24 hours later. Ketamine metabolite II levels were lower with a peak of 515 ng/ml in approximately 60 minutes to 13 to 27 ng/ml 24 hours later. Recovery from anesthesia was related to the first two phases of rapid redistribution of ketamine. The plasma levels of the two ketamine metabolites were first detectable approximately 5 minutes after ketamine injection. Their relatively low levels throughout ketamine anesthesia and postanesthesia do not correlate with recovery from anesthesia. CSTRIP and NONLIN analysis indicated that a three-exponential equation best approximated the data obtained. It is concluded that a three-compartment open model best approximates ketamine pharmacokinetics in these patients.