Age-Stratified Pharmacokinetics of Ketorolac Tromethamine in Pediatric Surgical Patients
Dsida R, Wheeler M, Birmingham P, et al. Anesthesia & Analgesia 2002; 94: 266-270.
Review: The goal of the study was to examine the pharmacokinetics of ketorolac in children to determine whether there are age-related pharmacokinetic differences. The study consisted initially of 43 patients, aged 1- 16 years, American Society of Anesthesiologists physical status I,II, or III, weighed from 10.9 to 80 kg, undergoing elective orthopedic or urologic procedures. Patients were stratified into four age groups: 1-3 yr, 4-7 yr, 8-11 yr, and 12-16 yr. None of the patients had a history of hepatic, renal, or cardiac disease. By the end of the study, sufficient data had been obtained on 36 patients.
Following the induction of general anesthesia, two intravenous catheters were inserted: 1) for fluid and drug administration and 2) for blood sampling. After completion of the operation and following adequate hemostasis, ketorolac tromethamine (0.5mg/kg) was given as an intravenous bolus. No dose administered was greater than 30mg. A 2-ml blood sample was obtained prior to administering ketorolac tromethamine and then subsequent samples were drawn at 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, 480, and 600 minutes following administration of the drug. Blood samples were centrifuged and the plasma was separated and frozen until further analysis.
Plasma ketorolac concentrations were determined by a liquid chromatography technique developed in the investigators' laboratory. The plasma ketorolac concentration-versus-time relationships were examined in the four age groups. Sampling took place over a period of approximately 10 hours with an average of 13 blood samples. The mean plasma ketorolac concentration-versus-time relationships following administration of 0.5mg/kg IV in the four age groups proved to be very similar. This is of particular significance in the first 6 hours following drug administration. On the contrary, differences were observed for the four age groups based on the nonweight-normalized pharmacokinetic variables. These variables included volume of distribution, peripheral distribution volume, volume of distribution at steady state, and elimination clearance.
Following final analysis of the data, this study suggest that weight-normalized pharmacokinetic variables for ketorolac are not different in children aged 1 to 16 years. Previous studies of ketorolac pharmacokinetics in the pediatric population have had variable results
Comment: This study is the first to demonstrate that following a single dose of ketorolac (0.5mg/kg) IV, plasma concentrations in the adult therapeutic concentration range will occur for six hours in most children before redosing is necessary. There is no evidence to suggest that either larger weight-adjusted doses or shorter dosing intervals are required in children. The results appear promising. If no contraindications exist from both the patient and surgical perspectives, then ketorolac tromethamine is worth consideration.
Reviewed by: Cheryl K. Gooden, MD
Mount Sinai Medical Center
New York, NY
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