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Pharmacokinetics-Based Pediatric Dose Evaluation and Optimization Using Saliva - A Case Study.

Anliker-Ort, M; Rodieux, F; Ziesenitz, VC; Atkinson, A; Bielicki, JA; Erb, TO; Gürtler, N; Holland-Cunz, S; Duthaler, U; Rudin, D; et al. Anliker-Ort, M; Rodieux, F; Ziesenitz, VC; Atkinson, A; Bielicki, JA; Erb, TO; Gürtler, N; Holland-Cunz, S; Duthaler, U; Rudin, D; Haschke, M; van den Anker, J; Pfister, M; Gotta, V (2024) Pharmacokinetics-Based Pediatric Dose Evaluation and Optimization Using Saliva - A Case Study. J Clin Pharmacol, 64 (7). pp. 810-819. ISSN 1552-4604 https://doi.org/10.1002/jcph.2428
SGUL Authors: Bielicki, Julia Anna

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Abstract

Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off-label in infants. Six plasma and 6 saliva PK sample collections were scheduled after a single intravenous dose of 10 mg/kg metamizole. Plasma/saliva pharmacometric (PMX) modeling of the active metabolites 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA) was performed. Various reduced plasma sampling scenarios were evaluated by PMX simulations. Saliva and plasma samples from 25 children were included (age range, 5-70 months; weight range, 8.7-24.8 kg). Distribution of metamizole metabolites between plasma and saliva was without delay. Estimated mean (individual range) saliva/plasma fractions of 4-MAA and 4-AA were 0.32 (0.05-0.57) and 0.57 (0.25-0.70), respectively. Residual variability of 4-MAA (4-AA) in saliva was 47% (28%) versus 17% (11%) in plasma. A simplified sampling scenario with up to 6 saliva samples combined with 1 plasma sample was associated with similar PK parameter estimates as the full plasma sampling scenario. This case study with metamizole shows increased PK variability in saliva compared to plasma, compromising its suitability as single matrix for PK studies in infants. Nonetheless, rich saliva sampling can reduce the number of plasma samples required for PK characterization, thereby facilitating the conduct of PK studies to optimize dosing in pediatric patients.

Item Type: Article
Additional Information: © 2024 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: children, infants, metamizole, pharmacokinetics, pharmacometrics, saliva, children, infants, metamizole, pharmacokinetics, pharmacometrics, saliva, 1115 Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Clin Pharmacol
ISSN: 1552-4604
Language: eng
Dates:
DateEvent
25 June 2024Published
18 March 2024Published Online
17 February 2024Accepted
Publisher License: Creative Commons: Attribution-Noncommercial 4.0
Projects:
Project IDFunderFunder ID
M.H. 3188Swiss National Science Foundationhttp://dx.doi.org/10.13039/501100001711
UNSPECIFIEDDivision of Pediatric Pharmacology & Pharmacometrics of the University Children's Hospital Basel (UKBB)UNSPECIFIED
PubMed ID: 38497339
Web of Science ID: WOS:001186270200001
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/116415
Publisher's version: https://doi.org/10.1002/jcph.2428

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