The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis

Mohammed, Baba Sulemana; Engelhardt, Thomas; Hawwa, Ahmed F.; Cameron, Gary; McLay, James S.

doi:10.1111/jphp.12418

Cited by 6 publications

(8 citation statements)

References 27 publications

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“…Previous studies in different patient groups have reported significantly higher pharmacokinetic parameters for the S‐ than the R‐enantiomer . In the current study, similar patterns were found: the typical clearance value of the S‐enantiomer was over threefold higher compared with the R‐enantiomer.…”

Section: Discussionsupporting

confidence: 88%

Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

Välitalo

Kemppainen

Kulo

et al. 2017

Brit J Clinical Pharma

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Section: Discussionsupporting

confidence: 88%

Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

Välitalo

Kemppainen

Kulo

et al. 2017

Brit J Clinical Pharma

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“…Data from three previously published studies of the pharmacokinetics of intravenous ketorolac in children were combined to assess the population pharmacokinetics of an intravenous bolus of ketorolac (0.5 mg . kg −1 ) administered for postoperative analgesia after elective surgery to children aged 2 months to 16 years …”

Section: Methodsmentioning

confidence: 99%

“…Following ethical approval by the North of Scotland Research Ethics Committees and authorization by the Medicines and Healthcare products Regulatory Agency‐UK, eleven children (aged 1.7‐15.6 years, weight 10.7‐67.4 kg, height 83‐165 cm, BMI 15.5‐32.1 kg . m −2 ) undergoing elective day case surgery were recruited for the pharmacokinetic analysis of intravenous ketorolac R(+) and S(−) enantiomers . General anesthesia was induced either intravenously with 3.5 mg .…”

Section: Methodsmentioning

confidence: 99%

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The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis

McLay

Engelhardt

Mohammed

et al. 2017

Pediatric Anesthesia

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“…The reason is our inability to include all published datasets in children. 13,26,27 Based on a systematic search, we identified and contacted all relevant research groups with data in children, and provided them with access to the study protocol.…”

Section: Simulations To Investigate the Contribution Of S-ketorolacmentioning

confidence: 99%

Impact of enantiomer‐specific changes in pharmacokinetics between infants and adults on the target concentration of racemic ketorolac: A pooled analysis

Cloesmeijer

Esdonk

Lynn

et al. 2020

Brit J Clinical Pharma

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Ketorolac is a nonsteroidal anti-inflammatory racemic drug with analgesic effects only attributed to its S-enantiomer. The aim of this study is to quantify enantiomer-specific maturational pharmacokinetics (PK) of ketorolac and investigate if the contribution of both enantiomers to the total ketorolac concentration remains equal between infants and adults or if a change in target racemic concentration should be considered when applied to infants. Methods: Data were pooled from 5 different studies in adults, children and infants, with 1020 plasma concentrations following single intravenous ketorolac administration. An allometry-based enantiomer-specific population PK model was developed with NONMEM 7.3. Simulations were performed in typical adults and infants to investigate differences in Sand R-ketorolac exposure. Results: Sand R-ketorolac PK were best described with a 3-and a 2-compartment model, respectively. The allometry-based PK parameters accounted for changes between populations. No maturation function of ketorolac clearance could be identified. All model parameters were estimated with adequate precision (relative standard error <50%). Single dose simulations showed that a previously established analgesic concentration at half maximal effect in adults of 0.37 mg/L, had a mean S-ketorolac concentration of 0.057 mg/L, but a mean S-ketorolac concentration of 0.046 mg/L in infants. To match the effective adult S-ketorolac-concentration (0.057 mg/L) in typical infants, the EC 50-racemic should be increased to 0.41 mg/L. Conclusion: Enantiomer-specific changes in ketorolac PK yield different concentrations and Sand R-ketorolac ratios between infants and adults at identical racemic concentrations. These PK findings should be considered when studies on maturational pharmacodynamics are considered.

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The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis

Abstract: Only body weight influenced the PK parameters for R(+) and S(-) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1 , V2 ).

Cited by 6 publications

References 27 publications

Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

Body weight, gender and pregnancy affect enantiomer‐specific ketorolac pharmacokinetics

The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis

Impact of enantiomer‐specific changes in pharmacokinetics between infants and adults on the target concentration of racemic ketorolac: A pooled analysis

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