Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study
PurposeThe prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants < 1 year. We aimed to assess the pharmacokinetics of the main metabolites of metamizole in children aged 3-72 months.MethodsA single dose of 10 mg/kg metamizole was adm...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
07 August 2019
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| In: |
European journal of clinical pharmacology
Year: 2019, Volume: 75, Issue: 11, Pages: 1491-1502 |
| ISSN: | 1432-1041 |
| DOI: | 10.1007/s00228-019-02720-2 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1007/s00228-019-02720-2
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| Author Notes: | Victoria C. Ziesenitz, Frédérique Rodieux, Andrew Atkinson, Carole Borter, Julia A. Bielicki, Manuel Haschke, Urs Duthaler, Fabio Bachmann, Thomas O. Erb, Nicolas Gürtler, Stefan Holland-Cunz, Johannes N. van den Anker, Verena Gotta, Marc Pfister |
| Summary: | PurposeThe prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants < 1 year. We aimed to assess the pharmacokinetics of the main metabolites of metamizole in children aged 3-72 months.MethodsA single dose of 10 mg/kg metamizole was administered intravenously for postoperative analgesia. Pharmacokinetic samples were drawn at predefined time points. Pharmacokinetics of the main active metabolite 4-methylaminoantipyrine and three other metabolites was characterized by both non-compartmental and population pharmacokinetic analysis. AUC0-inf of 4-methylaminoantipyrine was calculated by non-compartmental analysis for two age cohorts (3-23 months, 2-6 years) and compared with the 80-125% range of adult dose-adjusted reference exposure (AUCref). Population pharmacokinetic analysis investigated age and weight dependency of the pharmacokinetics and optimal dosing strategies to achieve equivalent adult exposure.ResultsA total of 25 children aged 5 months-5.8 years (7.8-24.8 kg) with at least one concentration sample were included; 19 children had ≥ 5 predefined samples up to 10 h after metamizole dose administration. AUC0-inf of 4-methylaminoantipyrine in children 2-6 years was 29.9 mg/L/h (95% CI 23.4-38.2), significantly lower than AUCref (80-125% range 39.2-61.2 mg/L/h). AUC0-inf of 4-methylaminoantipyrine in infants < 2 years was 43.6 mg/L/h (95% CI 15.8-119.0), comparable with AUCref, while infants < 12 months showed increased exposure. Observed variability could be partially explained by covariates weight and age.ConclusionsAge-related changes in pharmacokinetics of 4-methylaminoantipyrine requires reduced weight-based IV dosing in infants < 1 year compared with infants and children up to 6 years (5 versus 10-20 mg/kg) to achieve equivalent adult exposure.Trial registrationClinicalTrials.gov identifier: NCT02660177. |
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| Item Description: | Gesehen am 12.12.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1432-1041 |
| DOI: | 10.1007/s00228-019-02720-2 |