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Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria
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Rekke forfattare: 152016 (engelsk)Inngår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 214, nr 8, s. 1243-1251Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background. The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely used treatment for malaria, artemether-lumefantrine, has not been adequately characterized in young children. Methods. Capillary whole-blood lumefantrine concentration and treatment outcomes were determined in 105 Ugandan children, ages 6 months to 2 years, who were treated for 249 episodes of Plasmodium falciparum malaria with artemether-lumefantrine. Results. Population pharmacokinetics for lumefantrine used a 2-compartment open model with first-order absorption. Age had a significant positive correlation with bioavailability in a model that included allometric scaling. Children not receiving trimethoprim-sulfamethoxazole with capillary whole blood concentrations <200 ng/mL had a 3-fold higher hazard of 28-day recurrent parasitemia, compared with those with concentrations >200 ng/mL (P =. 0007). However, for children receiving trimethoprim-sulfamethoxazole, the risk of recurrent parasitemia did not differ significantly on the basis of this threshold. Day 3 concentrations were a stronger predictor of 28-day recurrence than day 7 concentrations. Conclusions. We demonstrate that age, in addition to weight, is a determinant of lumefantrine exposure, and in the absence of trimethoprim-sulfamethoxazole, lumefantrine exposure is a determinant of recurrent parasitemia. Exposure levels in children aged 6 months to 2 years was generally lower than levels published for older children and adults. Further refinement of artemether-lumefantrine dosing to improve exposure in infants and very young children may be warranted. © 2016 The Author.

sted, utgiver, år, opplag, sider
2016. Vol. 214, nr 8, s. 1243-1251
Emneord [en]
Malaria; population pharmacokinetics; lumefantrine; artemisinin combination therapy; antimalarial; nonlinear mixed effects modeling; pharmacodynamics; trimethoprim-sulfamethoxazole
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Identifikatorer
URN: urn:nbn:se:du-23296DOI: 10.1093/infdis/jiw338ISI: 000386147200021PubMedID: 27471317Scopus ID: 2-s2.0-84990929765OAI: oai:DiVA.org:du-23296DiVA, id: diva2:1040768
Tilgjengelig fra: 2016-10-28 Laget: 2016-10-28 Sist oppdatert: 2019-07-01bibliografisk kontrollert

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