title: The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria.
abstract: OBJECTIVE
  Intravenous artesunate is commonly used in the emergency treatment of patients with severe falciparum malaria in Asia. The choice of doses used has been empirical. To inform dosage recommendations we assessed the pharmacokinetics of intravenous artesunate after the first dose.
  
  
  METHODS
  As part of a clinical trial of artesunate in adults with severe falciparum malaria in western Thailand, we assayed plasma concentrations of artesunate and the principal biologically active metabolite dihydroartemisinin (DHA) in 17 patients given an initial dose of 2.4 mg/kg body weight of intravenous artesunate. Drug levels were measured using high performance liquid chromatography with mass spectroscopy-electrospray ionisation detection.
  
  
  RESULTS
  Median (range) observed DHA Cmax was 2128 (513-5789) nmol/L, elimination half-life was 0.34 (0.14-0.87) h, and the time to the last detectable DHA was 2 h.
  
  
  CONCLUSIONS
  The large inter-individual variability (10 fold) in DHA Cmax and AUC in patients with potentially lethal, severe malaria, suggests that 2.4 mg/kg should be the minimum daily dose in severe malaria.
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Karen I
authors.initials: KI
authors.lastname: Barnes
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Alicia C
authors.initials: AC
authors.lastname: Evans
authors.forename: Wirongrong
authors.initials: W
authors.lastname: Chierakul
authors.forename: Ronatrai
authors.initials: R
authors.lastname: Ruangveerayuth
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000077332:Artesunate; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004563:Electrochemistry / Q000379:methods; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010865:Pilot Projects; D011803:Quinine / Q000493:pharmacokinetics / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013785:Thailand
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol; D011803:Quinine