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Pharmacometric evaluation of pre‐referral rectal artesunate in children with severe malaria

IMPACT SIGNAL71/100
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Information from the abstract

AIMS: Parenteral artesunate is the preferred first-line treatment for severe malaria. Pre-referral rectal artesunate suppositories are recommended where parenteral treatment is inaccessible. In this study, we compared dihydroartemisinin exposure and model-predicted early parasite clearance following rectal artesunate and intravenous artesunate in African children with severe malaria. METHODS: A total of 82 African children with severe malaria participated in a randomized crossover study in Democratic Republic of Congo. Forty children received rectal artesunate (10 mg/kg) while the other 42 received intravenous artesunate (2.4 mg/kg) as the first intervention, and then the other route of administration for the second dose. Blood samples were drawn for drug quantification, and nonlinear mixed-effects modelling was used to evaluate the pharmacokinetic properties of intravenous and rectal artesunate and to simulate expected parasite clearance associated with these routes of administration. RESULTS: The mean individually estimated rectal bioavailability of artesunate was 21% but was highly variable (IQR: 8%-35%). Plasma exposure to dihydroartemisinin-the principal and bioactive metabolite of artesunate-did not differ significantly between rectal and intravenous administration. Predicted parasite reduction over the first 12 h was similar for both routes, consistent with previously reported clinical benefits of rectal artesunate. CONCLUSIONS: These findings support the 10-mg/kg dose of rectal artesunate as a pre-referral intervention, which should be more widely deployed in malaria-endemic areas.

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Why this record is monitored

This record has an Impact Signal of 71/100 based on recency, source, collaboration, and bibliographic signals. It prioritizes monitoring and is not a judgment of research quality.

Related topics: Malaria Research and Control · Parasites and Host Interactions · Pharmaceutical Quality and Counterfeiting

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Thai researcher and institutional participation

Ayorinde Adehin · Caterina Fanello · Nicholas J. White · Nicholas Day · Richard M. Hoglund · Joel Tärning · Mahidol University · Mahidol Oxford Tropical Medicine Research Unit

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Data limitations

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