ArticleBritish journal of clinical pharmacology2019
Development of a physiologically based pharmacokinetic model for mefloquine and its application alongside a clinical effectiveness model to select an optimal dose for prevention of malaria in young Caucasian children.
Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Application of Pharmacometric Modelling Towards Precise Dosing in Neonates, Infants and Toddlers: A Scoping Review.Clinical pharmacokinetics · 2026Review
- Pharmacokinetic and pharmacodynamic modeling of anti-plasmodial drugs mefloquine plus artesunate: insights on translational application.Antimicrobial agents and chemotherapy · 2026Article
- Use of population pharmacokinetic-pharmacodynamic modelling to inform antimalarial dose optimization in infants.British journal of clinical pharmacology · 2025Review
- Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Exploring inter-ethnic and inter-patient variability and optimal dosing of osimertinib: a physiologically based pharmacokinetic modeling approach.Frontiers in pharmacology · 2024Article
- Physiologically-based pharmacokinetic modeling for optimal dosage prediction of olaparib when co-administered with CYP3A4 modulators and in patients with hepatic/renal impairment.Scientific reports · 2023Article
- Predicting the correct dose in children: Role of computational Pediatric Physiological-based pharmacokinetics modeling tools.CPT: pharmacometrics & systems pharmacology · 2023Review
- A comparison of different methods for the first-in-pediatric dose selection.Journal of clinical and translational research · 2022Article
- Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development.AAPS PharmSciTech · 2021Review
- Development of a physiologically based pharmacokinetic model for mefloquine and its application alongside a clinical effectiveness model to select an optimal dose for prevention of malaria in young Caucasian children.British journal of clinical pharmacology · 2019Article
- Implementation of a Physiologically Based Pharmacokinetic Modeling Approach to Guide Optimal Dosing Regimens for Imatinib and Potential Drug Interactions in Paediatrics.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo predict the optimal chemoprophylactic dose of mefloquine in infants of 5-10 kg using physiologically based pharmacokinetic (PBPK) and clinical effectiveness models.
methodsThe PBPK model was developed in Simcyp version 14.1 and verified against clinical pharmacokinetic data in adults; the final model, accounting for developmental physiology and enzyme ontogeny was then applied in the paediatric population. The clinical effectiveness model utilized real-world chemoprophylaxis data with stratification of output by age and including infant data from the UK population.
resultsPBPK simulations in infant populations depend on the assumed fraction of mefloquine metabolized by CYP3A4 (0.47, 0.95) and on the associated CYP3A4 ontogeny (Salem, Upreti). However, all scenarios suggest that a dose of 62.5 mg weekly achieves or exceeds the exposure in adults following a 250 mg weekly dose and results in a minimum plasma concentration of 620 ng ml
conclusionsThe PBPK and clinical effectiveness models are mutually supportive and suggest a prophylactic dose of 62.5 mg weekly in the Caucasian 5-10 kg infant population travelling to endemic countries. This dual approach offers a novel route to dose selection in a vulnerable population, where clinical trials would be difficult to conduct.
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