We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacokinetics‐Based Pediatric Dose Evaluation and Optimization Using Saliva – A Case Study.
- Authors
Anliker‐Ort, Marion; Rodieux, Frédérique; Ziesenitz, Victoria C.; Atkinson, Andrew; Bielicki, Julia A.; Erb, Thomas O.; Gürtler, Nicolas; Holland‐Cunz, Stefan; Duthaler, Urs; Rudin, Deborah; Haschke, Manuel; van den Anker, John; Pfister, Marc; Gotta, Verena
- 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.
- Subjects
SALIVA analysis; RESEARCH funding; DESCRIPTIVE statistics; ANALGESICS; INTRAVENOUS therapy; METABOLITES; BLOOD plasma; PHARMACOKINETICS; PAIN management; POSTOPERATIVE period; CONFIDENCE intervals; DATA analysis software; CHILDREN
- Publication
Journal of Clinical Pharmacology, 2024, Vol 64, Issue 7, p810
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1002/jcph.2428