Ketorolac penetration into the cerebrospinal fluid of humans

To determine the cerebrospinal fluid (CSF): total plasma concentration ratio of ketorolac tromethamine following a single intramuscular (IM) dose.

Open, single-dose, IM-administration study.

General operating theaters of a medical school hospital.

29 ASA physical status I and II patients scheduled to undergo elective surgery with spinal anesthesia.

Patients were premedicated with ketorolac 90 mg IM formulated as 3 ml of a 3% solution. Between 1 and 4 1/2 hours later, an intravenous infusion of 500 ml of compound sodium lactate was begun. Lumbar puncture was then performed, and 2 ml of CSF was collected prior to administration of the spinal anesthetic. In addition, a 5 ml sample of venous blood was taken within 5 minutes of the CSF sample.

Simultaneous plasma and CSF concentrations of ketorolac were measured between 62 and 277 minutes following IM administration in 29 patients undergoing spinal anesthesia. The CSF concentrations were on the order of 1,000 times less than the total plasma concentrations; free concentrations of ketorolac in plasma were estimated to be about 10 times more than those in CSF. There appeared to be no constant time factor relating the appearance of ketorolac in the CSF to its plasma concentration following IM administration.

Although the sensitivity of central prostaglandin synthetase systems to inhibition is unknown, it is unlikely from this pharmacokinetic data that there is a major central mechanism of analgesia for ketorolac.