The pharmacokinetics of artemisinin suppositories in Vietnamese patients with malaria.
Eight male Vietnamese malaria patients received 600 mg of artemisinin in a single dose of 3 suppositories containing 200 mg each; 24 h later they received a single oral dose of mefloquine, 15 mg/kg. Plasma artemisinin concentrations were measured until 24 h after dosing, and parasites were counted until none could be detected. Artemisinin concentration versus time curves of all subjects were analysed with model-independent methods. Mean Cmax was 108 micrograms/L (SD = 60, range 29-169), mean tlag was 0.3 h (SD = 0), mean tmax was 6.5 h (SD = 3.9, range 2-14). By comparing the area under the concentration-time curve with that found in a previous study on oral artemisinin, average bioavailability relative to oral administration was estimated to be approximately 30%. Median parasite clearance time was 24 h (range 24-72). We concluded that therapeutic blood concentrations of artemisinin can be reached after rectal administration. There was a large inter-individual variation in blood concentrations attained. The dose given by rectal administration should probably be twice the usual oral dose, i.e., at least 20 mg/kg of body weight twice daily.
Koopmans
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Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands. R.P.Koopmans@amc.uva.nl
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de Vries
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van Boxtel
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D000285:Administration, Rectal; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000627:therapeutic use; D037621:Artemisinins; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010963:Plasmodium falciparum; D012717:Sesquiterpenes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome; D014744:Vietnam
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin; D015767:Mefloquine