Stereoselective pharmacokinetics of ketorolac in children, adolescents andadults

Background: Previous pharmacokinetic studies on racemic ketorolac using non stereoselective analytical methods have indicated that the plasma clearance of ketorolac is higher and the volume of distribution greater in children than in adults. The aim of this study was to study the stereoselective phar macokinetics of racemic ketorolac in children, adolescents and adults. Methods: 18 children (6-11 yrs), 18 adolescents (12-17 yrs) and 18 adults ( 18-44 yrs) participated in the study. At the end of eye surgery they were g iven intravenous racemic ketorolac tromethamine 0.5 mg/kg. Plasma samples w ere assayed for (R)- and (S)-ketorolac with high-pressure liquid chromatogr aphy. Clearance (CL), volume of distribution at steady state (V-ss) and eli mination (V-z) and elimination half-life (t(1/2,z)) were calculated with st andard methods. Incidence of side-effects were recorded. Results: CL, V-ss, V-z and t(1/2,z) were higher (P < 0.05) for (S)-ketorola c than for the (R)-enantiomer. V-ss of the active (S)-enantiomer was higher in children than in adolescents (P < 0.05) and adults (P < 0.001) but the values for CL were similar. Due to the higher volume of distribution, t(1/2 ,z) was also higher in children than in adults. The pharmacokinetics of the (R)-enantiomer were essentially unaffected by age. Conclusion: On a pharmacokinetic basis, the maintenance dose requirements o f ketorolac are similar in children, adolescents and adults.