Publication: Pharmacokinetic study of rectal artesunate in children with severe Malaria in Africa
Issued Date
2021-04-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85102993481
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.65, No.4 (2021)
Suggested Citation
Caterina Fanello, Richard M. Hoglund, Sue J. Lee, Daddy Kayembe, Pauline Ndjowo, Charlie Kabedi, Benjamin B. Badjanga, Phettree Niamyim, Joel Tarning, Charles Woodrow, Melba Gomes, Nick P. Day, Nicholas J. White, Marie A. Onyamboko Pharmacokinetic study of rectal artesunate in children with severe Malaria in Africa. Antimicrobial Agents and Chemotherapy. Vol.65, No.4 (2021). doi:10.1128/AAC.02223-20 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/78313
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Title
Pharmacokinetic study of rectal artesunate in children with severe Malaria in Africa
Abstract
When severe malaria is suspected in children, the WHO recommends pretreatment with a single rectal dose of artesunate before referral to an appropriate facility. This was an individually randomized, open-label, 2-arm, crossover clinical trial in 82 Congolese children with severe falciparum malaria to characterize the pharmacokinetics of rectal artesunate. At admission, children received a single dose of rectal artesunate (10 mg/kg of body weight) followed 12 h later by intravenous artesunate (2.4 mg/kg) or the reverse order. All children also received standard doses of intravenous quinine. Artesunate and dihydroartemisinin were measured at 11 fixed intervals, following 0- and 12-h drug administrations. Clinical, laboratory, and parasitological parameters were measured. After rectal artesunate, artesunate and dihydroartemisinin showed large interindividual variability (peak concentrations of dihydroartemisinin ranged from 5.63 to 8,090 nM). The majority of patients, however, reached previously suggested in vivo IC50 and IC90 values (98.7% and 92.5%, respectively) of combined concentrations of artesunate and dihydroartemisinin between 15 and 30 min after drug administration. The median (interquartile range [IQR]) time above IC50 and IC90 was 5.68 h (2.90 to 6.08) and 2.74 h (1.52 to 3.75), respectively. The absolute rectal bioavailability (IQR) was 25.6% (11.7 to 54.5) for artesunate and 19.8% (10.3 to 35.3) for dihydroartemisinin. The initial 12-h parasite reduction ratio was comparable between rectal and intravenous artesunate: median (IQR), 84.3% (50.0 to 95.4) versus 69.2% (45.7 to 93.6), respectively (P = 0.49). Despite large interindividual variability, rectal artesunate can initiate and sustain rapid parasiticidal activity in most children with severe falciparum malaria while they are transferred to a facility where parenteral artesunate is available. (This study has been registered at ClinicalTrials.gov under identifier NCT02492178.)
