Population Pharmacokinetics and Pharmacodynamics of Artemether and Lumefantrine during Combination Treatment in Children with Uncomplicated Falciparum Malaria in Tanzania
| العنوان: | Population Pharmacokinetics and Pharmacodynamics of Artemether and Lumefantrine during Combination Treatment in Children with Uncomplicated Falciparum Malaria in Tanzania |
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| المؤلفون: | Andreas Mårtensson, Zul Premji, Pedro Gil, Sabina Dahlström, Michael Ashton, Anna Färnert, Anna Annerberg, Anders Björkman, Billy Ngasala, Sofia Friberg Hietala, Niklas Lindegardh |
| المصدر: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| بيانات النشر: | American Society for Microbiology, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, medicine.medical_treatment, Pharmacology, Tanzania, Trial, Body Temperature, Plasma, chemistry.chemical_compound, 0302 clinical medicine, Pharmacology (medical), Artemether, Malaria, Falciparum, Child, Diagnosis & treatment, Asymptomatic children, 0303 health sciences, biology, Artemisinins, Dynamics, 3. Good health, Treatment Outcome, Infectious Diseases, Ethanolamines, Child, Preschool, Artemisinin, Female, medicine.drug, Plasmodium-Falciparum, Efficacy, 030231 tropical medicine, Dihydroartemisinin, Lumefantrine, Benflumetol, Antimalarials, 03 medical and health sciences, Pharmacokinetics, parasitic diseases, medicine, Humans, Fluorenes, Healthy-subjects, 030306 microbiology, business.industry, Infant, Plasmodium falciparum, biology.organism_classification, medicine.disease, NONMEM, chemistry, Pharmacodynamics, business, Malaria, Dose pharmacokinetics |
| الوصف: | The combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were included in the model of the parasite dynamics. The population pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine were modeled in NONMEM. The distribution of artemether was described by a two-compartment model with a rapid absorption and elimination through metabolism to dihydroartemisinin. Dihydroartemisinin concentrations were adequately illustrated by a one-compartment model. The pharmacokinetics of artemether was time dependent, with typical oral clearance increasing from 2.6 liters/h/kg on day 1 to 10 liters/h/kg on day 3. The pharmacokinetics of lumefantrine was sufficiently described by a one-compartment model with an absorption lag time. The typical value of oral clearance was estimated to 77 ml/h/kg. The proposed semimechanistic model of parasite dynamics, while a rough approximation of the complex interplay between malaria parasite and the human host, adequately described the early effect of ARM and DHA concentrations on the parasite density in malaria patients. However, the poor precision in some parameters illustrates the need for further data to support and refine this model. Sida [SWE-2005 017]; Wellcome Trust-Mahidol University [077166/Z/05/Z]; Wellcome Trust of Great Britain info:eu-repo/semantics/publishedVersion |
| وصف الملف: | application/pdf |
| تدمد: | 1098-6596 0066-4804 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26cc8e60593bd09e37e4baa1d21971c7Test https://doi.org/10.1128/aac.00252-10Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....26cc8e60593bd09e37e4baa1d21971c7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10986596 00664804 |
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