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|Title: ||Pharmacokinetics of artemether-lumefantrine and artesunate/amodiaquine in children in Kampala, Uganda|
|Authors: ||Mwesigwa, Julia|
Kalyango, Joan N.
Clark, Tamara D.
Rosenthal, Philip J.
Kamya, Moses R.
|Keywords: ||World Health Organization (WHO)|
Artemisinin-based combination therapies (ACT)
|Issue Date: ||Dec-2008 |
|Abstract: ||The World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACT) for the treatment of uncomplicated malaria. The two most widely adopted ACT regimens are artemether/lumetantrine (AL) and amodiaquine/artesunate (AQ/AS). Pharmacokinetic (PK) data informing optimum dosing of these drug regimens is limited, especially in children. We evaluated PK parameters in
Ugandan children aged 5-13 years with uncomplicated malaria treated with AL (n=20) or AQ/AS (n=21), with intensive venous sampling at 0, 2, 4, 8, 24 and 120 hours following the last dose of 3 day regimens of AL (twice daily) or AQ/AS (once daily). Artesunate achieved an estimated Cmax of 51 ng/ml and AUC0-∞ of 113h-ng/ml and its active metabolite dihydroartemisinin (DHA) achieved a geometric mean Cmax of 473 ng/ml and AUC0-∞ 1404 h-ng/ml; while artemether (AR)/DHA exhibited a Cmax of 34/119 ng/ml and AUC0-∞168/382h-ng/ml, respectively. For lumefantrine (LR), Cmax and AUC0-∞ were 6757 ng/mL and 210h-μg/ml. For amodiaquine (AQ) and its active metabolite, desethylamodiaquine (DEAQ), Cmax and AUC0-∞ were 5.2ng/ml and 39.3h-ng/ml for AQ; 235 ng/ml and 148h-μg/ml for DEAQ. Comparison to prior adult data suggests that LR exposure is lower in children, that AQ/DEAQ exposure is similar in children and adults. For the artemisinin derivatives, differences between children and adults are variable and drug specific. PK results generated in children must be considered to optimize dosing strategies for these widely utilized ACT regimens.|
|Appears in Collections:||Research Articles (Health-Sciences)|
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