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Following an intensive sampling protocol, samples were assayed for ARTS and its primary active metabolite, dihydroartemisinin (DHA), by liquid chromatography-mass spectrometry. A population pharmacokinetic model was developed to describe the data. Following administration of the first dose, the mean maximal concentrations of ARTS and DHA were 1,085 nmol\/liter at 0.9 h and 2,525 nmol\/liter at 2.3 h, respectively. The absorption half-life for ARTS was 2.3 h, and the conversion half-life (ARTS to DHA) was 0.27 h, while the elimination half-life of DHA was 0.71 h. The mean common volumes of distribution for ARTS and DHA relative to bioavailability were 42.8 and 2.04 liters\/kg, respectively, and the mean clearance values relative to bioavailability were 6 and 2.2 liters\/h\/kg for ARTS and DHA, respectively. Substantial interpatient variability was observed, and the bioavailability of the second dose relative to that of the first was estimated to be 0.72. The covariates age, sex, and \u03b1-thalassemia genotype were not influential in the pharmacokinetic model development; but the inclusion of weight as a covariate significantly improved the performance of the model. An ARTS suppositories dose of 10 of 20 mg\/kg is appropriate for use in children with uncomplicated malaria.<\/jats:p>","DOI":"10.1128\/aac.48.8.2966-2972.2004","type":"journal-article","created":{"date-parts":[[2004,7,23]],"date-time":"2004-07-23T18:45:20Z","timestamp":1090608320000},"page":"2966-2972","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Disposition of Artesunate and Dihydroartemisinin after Administration of Artesunate Suppositories in Children from Papua New Guinea with Uncomplicated Malaria"],"prefix":"10.1128","volume":"48","author":[{"given":"Harin A.","family":"Karunajeewa","sequence":"first","affiliation":[{"name":"School of Medicine and Pharmacology, University of Western Australia, Crawley"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth F.","family":"Ilett","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacology, University of Western Australia, Crawley"},{"name":"Clinical Pharmacology &amp; Toxicology Laboratory, The Western Australian Centre for Pathology &amp; Medical Research, Nedlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kitiya","family":"Dufall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adedayo","family":"Kemiki","sequence":"additional","affiliation":[{"name":"Modilon General Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moses","family":"Bockarie","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Alpers","sequence":"additional","affiliation":[{"name":"Curtin University of Technology, Bentley, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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