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Population pharmaco...
Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria
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Tchaparian, E. (författare)
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Sambol, N.C. (författare)
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Arinaitwe, E. (författare)
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McCormack, S.A. (författare)
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Bigira, V. (författare)
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Wanzira, H. (författare)
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Blessborn, Daniel (författare)
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- Bergqvist, Yngve (författare)
- Högskolan Dalarna,Medicinsk vetenskap
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Aweeka, F.T. (författare)
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Parikh, S. (författare)
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(creator_code:org_t)
- 2016-07-28
- 2016
- Engelska.
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 214:8, s. 1243-1251
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- Malaria; population pharmacokinetics; lumefantrine; artemisinin combination therapy; antimalarial; nonlinear mixed effects modeling; pharmacodynamics; trimethoprim-sulfamethoxazole
- Hälsa och välfärd
- Health and Welfare
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Tchaparian, E.
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Sambol, N.C.
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Arinaitwe, E.
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McCormack, S.A.
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Bigira, V.
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Wanzira, H.
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visa fler...
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Blessborn, Danie ...
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Bergqvist, Yngve
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Aweeka, F.T.
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Parikh, S.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
- Artiklar i publikationen
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Journal of Infec ...
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Högskolan Dalarna