Stereoselective pharmacokinetics of ketorolac in children, adolescents and adults.

Abstract

Previous pharmacokinetic studies on racemic ketorolac using nonstereoselective 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 pharmacokinetics of racemic ketorolac in children, adolescents and adults. 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 given intravenous racemic ketorolac tromethamine 0.5 mg/kg. Plasma samples were assayed for (R)- and (S)-ketorolac with high-pressure liquid chromatography. Clearance (CL), volume of distribution at steady state (Vss) and elimination (Vz) and elimination half-life (t1/2,z) were calculated with standard methods. Incidence of side-effects were recorded. CL, Vss, Vz and t1/2,z were higher (P<0.05) for (S)-ketorolac than for the (R)-enantiomer. Vss 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, t1/2,z was also higher in children than in adults. The pharmacokinetics of the (R)-enantiomer were essentially unaffected by age. On a pharmacokinetic basis, the maintenance dose requirements of ketorolac are similar in children, adolescents and adults.