Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children

Abstract

The higher clearance in children suggests that the weight-adjusted dose of ketorolac may have to be greater for children to achieve plasma concentrations comparable to those of adults. Because of the greater clearance and shorter half-life of S(-)-ketorolac, pharmacokinetic predictions based on racemic assays may overestimate the duration of pharmacologic effect. Enantiomeric pharmacokinetic differences are best explained by stereoselective plasma protein binding. Selective glucuronidation of the S(-) enantiomer suggests that stereoselective metabolism may also be a contributing factor.

Postoperative Ketorolac Tromethamine Use in Infants Aged 6–18 Months: The Effect on Morphine Usage, Safety Assessment, and Stereo-Specific Pharmacokinetics

“…In the infants and toddlers, both V 1 and V ␤ were significantly larger for S(Ϫ) ketorolac than for R(ϩ) ketorolac. Similar results were found in older children for V ␤ (7,8).…”

“…Because all infants and toddlers in this study were also receiving morphine for postoperative analgesia, an interaction affecting ketorolac's metabolism is possible. However, because combining ketorolac with opioids is the most (7,8). The elimination half-life of the analgesically active isomer occurs even more quickly in infants than in children.…”

Identification and structural characterization of in vivo metabolites of ketorolac using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS)

“…Adverse effect may even be related to trace level of metabolite accumulation as reported previously with some classes of compounds . Previously, some metabolites which are excreted as hydroxy KTC and KTC glucuronide in urine have been reported . However, no information exists in literature on identification and structural characterization of most of the KTC metabolites.…”

“…However, no information exists in literature on identification and structural characterization of most of the KTC metabolites. Only few HPLC and LC‐MS methods are available in the literature for the determination of KTC and KTC enantiomers in plasma …”

Recent applications of stereoselective chromatography

“…This type of selector has been used in the separation of the enantiomers of ketamine and its active metabolite norketamine, 30 bisoprolol, 31,32 lorazepam, 34 propranolol, 35 fluoxetine and its active metabolite norfluoxetine, 38 tramadol and O-demethyltramadol, 39 selfotel, 42 verapamil and norverapamil, 44 cisapride, 47 isradipine, 48 as well as thalidomide. 50 For all these drugs the developed methods have been sensitive and sufficiently reproducible for stereoselective monitoring of these agents in human plasma (serum or urine) during pharmacokinetic studies.…”