DDMODEL00000310: Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children

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Short description:
Population pharmacokinetics of piperaquine for seasonal malaria chemoprevention in young children in Burkina Faso
Original code
  • Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children.
  • Chotsiri P, Zongo I, Milligan P, Compaore YD, Somé AF, Chandramohan D, Hanpithakpong W, Greenwood B, Rosenthal PJ, White NJ, Ouédraogo JB
  • Nature communications, 1/2019, Volume 10, Issue 1, pages: 480
  • Faculty of Tropical Medicine, Department of Clinical Pharmacology, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, 10400, Thailand.
  • Young children are the population most severely affected by Plasmodium falciparum malaria. Seasonal malaria chemoprevention (SMC) with amodiaquine and sulfadoxine-pyrimethamine provides substantial benefit to this vulnerable population, but resistance to the drugs will develop. Here, we evaluate the use of dihydroartemisinin-piperaquine as an alternative regimen in 179 children (aged 2.33-58.1 months). Allometrically scaled body weight on pharmacokinetic parameters of piperaquine result in lower drug exposures in small children after a standard mg per kg dosage. A covariate-free sigmoidal EMAX-model describes the interval to malaria re-infections satisfactorily. Population-based simulations suggest that small children would benefit from a higher dosage according to the WHO 2015 guideline. Increasing the dihydroartemisinin-piperaquine dosage and extending the dose schedule to four monthly doses result in a predicted relative reduction in malaria incidence of up to 58% during the high transmission season. The higher and extended dosing schedule to cover the high transmission period for SMC could improve the preventive efficacy substantially.
Joel Tarning
Context of model development: Variability sources in PK and PD (CYP, Renal, Biomarkers); Combination Therapy Dose Selection;
Long technical model description: A detailed explanation of the model can be found in the published manuscript, Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children (published at nature communications);
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: A malaria infection during the first five years of age can have severe consequences and mortality rate due to malaria in these young children are more than 60%. Chemoprevention is one of the recommended strategies to combat malaria in this vulnerable population. The aim of this model was to describe the pharmacokinetic properties of piperaquine as a seasonal malaria chemoprevention in young children;
Modelling task in scope: estimation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Anti-infectives;
Annotations are correct.
This model is not certified.
  • Model owner: Joel Tarning
  • Submitted: Oct 3, 2019 9:54:42 AM
  • Last Modified: Oct 3, 2019 9:54:42 AM
  • Version: 4 public model Download this version
    • Submitted on: Oct 3, 2019 9:54:42 AM
    • Submitted by: Joel Tarning
    • With comment: Updated model annotations.