Megan Palmer, Yuanxi Zou, Anneke C. Hesseling, Louvina van der Laan, Ingrid Courtney, Aarti A. Kinikar, Naresh Sonkawade, Mandar Paradkar, Vandana Kulkarni, Dessa Jean O. Casalme, Melchor V. G. Frias, Heather Draper, Lubbe Wiesner, Mats O. Karlsson, Paolo Denti, Elin M. Svensson, Anthony J. Garcia-Prats
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Children were enrolled in South Africa, India and the Philippines. Intensive pharmacokinetic sampling was undertaken while children were taking the standard non-dispersible 400 mg moxifloxacin tablet formulation and repeated after switching to the novel dispersible formulation. Pharmacokinetic data were analysed using population pharmacokinetic modelling. Simulations were performed to evaluate moxifloxacin exposures in children compared to consensus adult reference exposures using current World Health Organization (WHO)-recommended doses and more recent model-based doses.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Thirty-six children were enrolled [median age 4.8 (range 0.4–15) years and weight 15.6 (range 6.9–42.1) kg]. A two-compartment disposition model with first-order elimination and delayed absorption was developed. The bioavailability of dispersible versus standard formulations fulfilled standard bioequivalence criterion (ratio 1.05 with 90% confidence interval 0.95–1.15). Simulations showed WHO-recommended doses achieved exposures similar to those in adults in children >10 kg, while children <10 kg may require 33%–56% higher doses to reach adult reference exposures.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Dosing recommendations for children can be the same for the dispersible paediatric and standard non-dispersible adult moxifloxacin formulation. The current WHO dosing recommendation risks underdosing moxifloxacin in children <10 kg. We propose optimized moxifloxacin doses for both formulations.</p>\n </section>\n </div>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 6","pages":"1853-1864"},"PeriodicalIF":3.0000,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bcp.70005","citationCount":"0","resultStr":"{\"title\":\"Population pharmacokinetics and dosing of dispersible moxifloxacin formulation in children with rifampicin-resistant tuberculosis\",\"authors\":\"Megan Palmer, Yuanxi Zou, Anneke C. Hesseling, Louvina van der Laan, Ingrid Courtney, Aarti A. Kinikar, Naresh Sonkawade, Mandar Paradkar, Vandana Kulkarni, Dessa Jean O. Casalme, Melchor V. G. Frias, Heather Draper, Lubbe Wiesner, Mats O. Karlsson, Paolo Denti, Elin M. Svensson, Anthony J. Garcia-Prats\",\"doi\":\"10.1002/bcp.70005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Moxifloxacin is a priority drug for treating rifampicin-resistant tuberculosis (RR-TB). We assessed the pharmacokinetics of a child-friendly, dispersible 100 mg tablet moxifloxacin formulation (dispersed in water) compared to the standard 400 mg non-dispersible formulation (crushed and suspended in water) in children and evaluated current dosing recommendations.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The CATALYST trial investigated the pharmacokinetics of moxifloxacin in children with RR-TB. Children were enrolled in South Africa, India and the Philippines. Intensive pharmacokinetic sampling was undertaken while children were taking the standard non-dispersible 400 mg moxifloxacin tablet formulation and repeated after switching to the novel dispersible formulation. Pharmacokinetic data were analysed using population pharmacokinetic modelling. Simulations were performed to evaluate moxifloxacin exposures in children compared to consensus adult reference exposures using current World Health Organization (WHO)-recommended doses and more recent model-based doses.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Thirty-six children were enrolled [median age 4.8 (range 0.4–15) years and weight 15.6 (range 6.9–42.1) kg]. A two-compartment disposition model with first-order elimination and delayed absorption was developed. The bioavailability of dispersible versus standard formulations fulfilled standard bioequivalence criterion (ratio 1.05 with 90% confidence interval 0.95–1.15). 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Population pharmacokinetics and dosing of dispersible moxifloxacin formulation in children with rifampicin-resistant tuberculosis
Aims
Moxifloxacin is a priority drug for treating rifampicin-resistant tuberculosis (RR-TB). We assessed the pharmacokinetics of a child-friendly, dispersible 100 mg tablet moxifloxacin formulation (dispersed in water) compared to the standard 400 mg non-dispersible formulation (crushed and suspended in water) in children and evaluated current dosing recommendations.
Methods
The CATALYST trial investigated the pharmacokinetics of moxifloxacin in children with RR-TB. Children were enrolled in South Africa, India and the Philippines. Intensive pharmacokinetic sampling was undertaken while children were taking the standard non-dispersible 400 mg moxifloxacin tablet formulation and repeated after switching to the novel dispersible formulation. Pharmacokinetic data were analysed using population pharmacokinetic modelling. Simulations were performed to evaluate moxifloxacin exposures in children compared to consensus adult reference exposures using current World Health Organization (WHO)-recommended doses and more recent model-based doses.
Results
Thirty-six children were enrolled [median age 4.8 (range 0.4–15) years and weight 15.6 (range 6.9–42.1) kg]. A two-compartment disposition model with first-order elimination and delayed absorption was developed. The bioavailability of dispersible versus standard formulations fulfilled standard bioequivalence criterion (ratio 1.05 with 90% confidence interval 0.95–1.15). Simulations showed WHO-recommended doses achieved exposures similar to those in adults in children >10 kg, while children <10 kg may require 33%–56% higher doses to reach adult reference exposures.
Conclusions
Dosing recommendations for children can be the same for the dispersible paediatric and standard non-dispersible adult moxifloxacin formulation. The current WHO dosing recommendation risks underdosing moxifloxacin in children <10 kg. We propose optimized moxifloxacin doses for both formulations.
期刊介绍：
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.
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