Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria
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.Capillary whole-blood lumefantrine concentration and treatment outcomes were determined in 105 Uganda...
| Váldodahkkit: | , , , , , , , , , , , , , , |
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| Materiálatiipa: | Journal article |
| Giella: | English |
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Oxford University Press
2016
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| _version_ | 1826259945103818752 |
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| author | Tchaparian, E Sambol, N Arinaitwe, E McCormack, S Bigira, V Wanzira, H Muhindo, M Creek, D Sukumar, N Blessborn, D Tappero, J Kakuru, A Bergqvist, Y Aweeka, F Parikh, S |
| author_facet | Tchaparian, E Sambol, N Arinaitwe, E McCormack, S Bigira, V Wanzira, H Muhindo, M Creek, D Sukumar, N Blessborn, D Tappero, J Kakuru, A Bergqvist, Y Aweeka, F Parikh, S |
| author_sort | Tchaparian, E |
| collection | OXFORD |
| description | 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.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.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.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. |
| first_indexed | 2024-03-06T18:57:50Z |
| format | Journal article |
| id | oxford-uuid:12775a58-bb47-48dc-a7cf-7fd9f1d522f4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:57:50Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:12775a58-bb47-48dc-a7cf-7fd9f1d522f42022-03-26T10:08:08ZPopulation pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malariaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:12775a58-bb47-48dc-a7cf-7fd9f1d522f4EnglishSymplectic Elements at OxfordOxford University Press2016Tchaparian, ESambol, NArinaitwe, EMcCormack, SBigira, VWanzira, HMuhindo, MCreek, DSukumar, NBlessborn, DTappero, JKakuru, ABergqvist, YAweeka, FParikh, SThe 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.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.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.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. |
| spellingShingle | Tchaparian, E Sambol, N Arinaitwe, E McCormack, S Bigira, V Wanzira, H Muhindo, M Creek, D Sukumar, N Blessborn, D Tappero, J Kakuru, A Bergqvist, Y Aweeka, F Parikh, S Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria |
| title | Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria |
| title_full | Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria |
| title_fullStr | Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria |
| title_full_unstemmed | Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria |
| title_short | Population pharmacokinetics and pharmacodynamics of lumefantrine in young Ugandan children treated with artemether-lumefantrine for uncomplicated malaria |
| title_sort | population pharmacokinetics and pharmacodynamics of lumefantrine in young ugandan children treated with artemether lumefantrine for uncomplicated malaria |
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