Key result
IV ketorolac shows similar clearance across ages but higher active S-enantiomer distribution volume in children.
Why the study?
Previous pharmacokinetic studies on racemic ketorolac using nonstereoselective methods indicated differences in clearance and volume of distribution between children and adults, but stereoselective pharmacokinetics across age groups were not studied.
Does age affect the stereoselective pharmacokinetics of intravenous racemic ketorolac in patients undergoing eye surgery?
Does age affect the stereoselective pharmacokinetics of intravenous racemic ketorolac in patients undergoing eye surgery?
The maintenance dose requirements of ketorolac are similar across children, adolescents, and adults due to similar clearance rates, despite differences in volume of distribution.
May inform pediatric ketorolac dosing considerations; leaves open need for efficacy and safety trials.
BACKGROUND: 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. 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 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. RESULTS: 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. CONCLUSION: On a pharmacokinetic basis, the maintenance dose requirements of ketorolac are similar in children, adolescents and adults.
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Hamunen et al. (1999) studied Eye surgery (n=54). Intravenous racemic ketorolac tromethamine vs. Adults and adolescents (age comparison) / (R)-enantiomer was evaluated on Stereoselective pharmacokinetics (Clearance, volume of distribution at steady state, elimination, and elimination half-life). Intravenous racemic ketorolac demonstrated similar clearance across age groups, although the volume of distribution of the active (S)-enantiomer was higher in children than adults (P<0.001).
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