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S(+)-ketamine Effect on Experimental Pain and Cardiac Output: A Population Pharmacokinetic-Pharmacodynamic Modeling Study in Healthy Volunteers
Anesthesiology, 09/14/09

Sigtermans M et al. – Low–dose ketamine behaves as an analgesic in the treatment of acute and chronic pain...Sex differences observed were restricted to pharmacokinetic model parameters, with a 20% greater elimination clearance of S(+)–ketamine and S(+)–norketamine in women resulting in higher drug plasma concentrations in men. S(+)–ketamine produced profound drug high and analgesia with six times greater potency in the heat pain than the electrical pain test. After ketamine–infusion, analgesia rapidly dissipated; in the heat pain test but not the electrical pain test, analgesia was followed by a period of hyperalgesia. Over the dose range tested, ketamine produced a 40–50% increase in cardiac output. A significant consistent contribution of S(+)–norketamine to overall effect was detected for none of the outcome parameters. S(+)–ketamine displays clinically relevant sex differences in its pharmacokinetics. It is a potent analgesic at already low plasma concentrations, but it is associated with intense side effects.

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