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


METHODS
Open, single-dose, IM-administration study.


METHODS
General operating theaters of a medical school hospital.


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Rice
A S
AS
Department of Anaesthetics, St. Thomas' Hospital, London, UK.
Lloyd
J
J
Bullingham
R E
RE
O'Sullivan
G
G
D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D000775:Anesthesia, Spinal; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007476:Ionophores / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D020911:Ketorolac Tromethamine; D008297:Male; D008875:Middle Aged; D011229:Preanesthetic Medication; D013997:Time Factors; D014046:Tolmetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid; D014325:Tromethamine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007476:Ionophores; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D014046:Tolmetin