Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
| Autor: | Samwel Gesase, Ilse C. E. Hendriksen, A Kent, Joel Tarning, Arjen M. Dondorp, Hugh Reyburn, L von Seidlein, George Mtove, Niklas Lindegardh, Martha M. Lemnge, Nicholas P. J. Day, Nicholas J. White |
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| Rok vydání: | 2013 |
| Předmět: |
Pediatrics
medicine.medical_specialty Time Factors 030231 tropical medicine Population Artesunate Injections Intramuscular Models Biological Severity of Illness Index Tanzania Drug Administration Schedule Antimalarials 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics parasitic diseases medicine Humans Tissue Distribution Pharmacology (medical) Dosing Malaria Falciparum Child education Pharmacology Volume of distribution 0303 health sciences education.field_of_study Dose-Response Relationship Drug 030306 microbiology business.industry Body Weight Area under the curve Infant Articles Artemisinins 3. Good health NONMEM Nonlinear Dynamics chemistry Child Preschool Pharmacodynamics Anesthesia business |
| Zdroj: | Clinical Pharmacology and Therapeutics |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/clpt.2013.26 |
| Popis: | Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria. A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years. All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2.4 mg/kg at 0, 12, and 24 h). Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM). A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA. Body weight significantly affected clearance and apparent volume of distribution (P < 0.001), resulting in lower ARS and DHA exposure levels in smaller children. An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model. © 2013 American Society for Clinical Pharmacology and Therapeutics. |
| Databáze: | OpenAIRE |
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