KETOROLAC PENETRATION INTO THE CEREBROSPINAL-FLUID OF HUMANS

Study Objective: To determine the cerebrospinal fluid (CSF): total pla sma concentration ratio of ketorolac tromethamine following a single i ntramuscular (IM) dose. Design: Open, single-dose, IM-administration s tudy. Setting: General operating theaters of a medical school hospital . Patients: 29 ASA physical status T and II patients scheduled to unde rgo elective surgery with spinal anesthesia. Interventions: Patients w ere premedicated with ketorolac 90 mg IM formulated as 3 ml of a 3% so lution. Between I and 41/2 hours later; an intravenous infusion of 500 ml of compound sodium lactate was begun. Lumbar puncture was then per formed, and 2 ml of CSF was collected prior to administration of the s pinal anesthetic. In addition, a 5 ml sample of venous blood was taken , within 5 minutes of the CSF sample. Measurements and Main Results: S imultaneous plasma and CSF concentrations of ketorolac were measured b etween 62 and 277 minutes following IM administration in 29 patients u ndergoing spinal anesthesia. The CSF concentrations were on the order of 1,000 times less than the total plasma concentrations;free concentr ations of ketorolac in plasma were estimated to be about 10 times more than those in CSF. There appeared to be no constant lime factor relat ing the appearance of ketorolac in the CSF to its plasma concentration following IM administration. Conclusion: Although the sensitivity of central prostaglandin synthetase systems to inhibition is unknown., it is unlikely from this pharmacokinetic data that there is a major cent ral mechanism of analgesia for Ketorolac.