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Pharmacokinetics-based pediatric dose evaluation and optimization using saliva - a case study

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 studie...

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Main Authors: Anliker-Ort, Marion (Author) , Rodieux, Frédérique (Author) , Ziesenitz, Victoria C. (Author) , Atkinson, Andrew (Author) , Bielicki, Julia A. (Author) , Erb, Thomas O. (Author) , Gürtler, Nicolas (Author) , Holland-Cunz, Stefan (Author) , Duthaler, Urs (Author) , Rudin, Deborah (Author) , Haschke, Manuel (Author) , van den Anker, John (Author) , Pfister, Marc (Author) , Gotta, Verena (Author)
Format: Article (Journal)
Language:English
Published: July 2024
In: Journal of clinical pharmacology
Year: 2024, Volume: 64, Issue: 7, Pages: 810-819
ISSN:1552-4604
DOI:10.1002/jcph.2428
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/jcph.2428
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jcph.2428
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Author Notes:Marion Anliker-Ort, PhD, Frédérique Rodieux, MD, Victoria C. Ziesenitz, MD, Andrew Atkinson, PhD, Julia A. Bielicki, MD, PhD, Thomas O. Erb, MD, Nicolas Gürtler, MD, Stefan Holland-Cunz, MD, Urs Duthaler, PhD, Deborah Rudin, PhD, Manuel Haschke, MD, John van den Anker, MD, PhD, FAAP, FCP, Marc Pfister, MD, PhD, FCP, and Verena Gotta, PhD
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Summary: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 Description:Veröffentlicht: 18. März 2024
Gesehen am 01.08.2024
Physical Description:Online Resource
ISSN:1552-4604
DOI:10.1002/jcph.2428

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