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

Abstract

The stereo-isomer-specific clearance of ketorolac in infants and toddlers (aged 6-18 mo) shows rapid elimination of the analgesic S(-) isomer. No adverse effects on surgical drain output, oximetry measured saturations, renal or hepatic function tests were seen. Simulation of single dosing at 0.5 or 1 mg/kg every 4 or 6 h does not lead to accumulation of S(-) ketorolac, the analgesic isomer, but does result in increases in R(+) ketorolac. Shorter dose intervals may be needed in infants older than 6 mo.

Ketorolac tromethamine: stereo‐specific pharmacokinetics and single‐dose use in postoperative infants aged 2–6 months

“…For parameter estimation, the model was parameterized in terms of clearance (CL), central volume of distribution (V1), inter‐compartmental clearance (Q), and peripheral volume of distribution (V2). The inter‐compartmental clearance, Q, was considered fixed across subjects based on the previous modeling results in the older infants (12). The model’s between‐subject variability structure (random effects on all parameters except inter‐compartmental clearance, and correlation between clearance and volume random effects) was left unchanged with respect to the one established for the older infants.…”

“…Ketorolac is administered as a racemic mixture with the S (−) isomer responsible for the analgesic effect in animal models. We previously reported on the stereo‐specific pharmacokinetics of S (−) and R (+) isomers of ketorolac for 37 infants aged 6–18 months studied after surgery (12). The infants aged 6–18 months rapidly clear the active S (−) isomer of ketorolac (elimination half‐life of 50 min), while the R (+) isomer clearance is slower.…”

“…This report includes infants aged 2–6 months. While safety and efficacy data are reported for the 2‐ to 6‐month‐old infants, to maximize the pharmacokinetic information, the data set previously reported for infants aged 6–18 months (12) receiving single‐dose IV ketorolac (25 of 37 infants) was combined with the pharmacokinetic values from these 2‐to 6‐month‐old infants, as has been proposed previously (15).…”

The Pharmacokinetics of Ketorolac After Single Postoperative Intranasal Administration in Adolescent Patients

“…Ketorolac has significant opioid-sparing effects 1,2 and is considered to be a useful postoperative analgesic medication. [3][4][5] Children may benefit from the use of ketorolac after surgery. An alternate route of administration that results in rapid onset would be useful in pediatric patients when IV access is not available or convenient.…”

Safety of opioid patch initiation in Australian residential aged care

“…The elimination half-life of ketorolac (Lynn et al, 2007), ibuprofen (Kyllonen et al, 2005) and diclofenac (Litalien & Jacqz-Aigrain, 2001) is longest in neonates, with the value in toddlers approaching that of adults. Rectal bioavailability of diclofenac is high in children (van der Marel et al, 2004).…”