title: The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria.
abstract: OBJECTIVE
  To obtain pharmacokinetic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.m. ARTS and rectal DHA administration.
  
  
  METHODS
  Twelve Vietnamese patients with uncomplicated falciparum malaria were randomized to receive either i.v. or i.m. ARTS (120 mg), with the alternative preparation given 8 h later in an open crossover design. A further 12 patients were given i.v. ARTS (120 mg) at 0 h and rectal DHA (160 mg) 8 h later.
  
  
  RESULTS
  Following i.v. bolus, ARTS had a peak concentration of 42 microm (16 mg l(-1), elimination t1/2 = 3.2 min, CL = 2.8 l h(-1) kg(-1) and V = 0.22 l kg(-1) . The Cmax for DHA was 9.7 microm (2.7 mg l(-1) ), t1/2 = 59 min, CL = 0.64 l h(-1) kg(-1) and V = 0.8 l kg(-1) . Following i.m. ARTS, Cmax was 2.3 microm (3.7 mg l(-1)), the apparent t1/2 = 41 min, CL = 2.9 l h(-1) kg(-1) and V = 2.6 l kg(-1). The relative bioavailability of DHA was 88%, Cmax was 4.1 microm (1.16 mg l(-1)) and t1/2 = 64 min. In the rectal DHA study, relative bioavailability of DHA was 16%.
  
  
  CONCLUSIONS
  For patients with uncomplicated falciparum malaria i.m. ARTS is a suitable alternative to i.v. ARTS, at equal doses. To achieve plasma DHA concentrations equivalent to parenteral administration of ARTS, rectal DHA should be given at approximately four-fold higher milligram doses. Further studies are needed to determine whether these recommendations can be applied to patients with severe malaria.
authors.affiliation: Department of Pharmacology, University of Western Australia, Nedlands 6009 Western Australia. kilett@receptor.pharm.uwa.edu.au
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Ilett
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Batty
authors.forename: Shane M
authors.initials: SM
authors.lastname: Powell
authors.forename: Tran Quang
authors.initials: TQ
authors.lastname: Binh
authors.forename: Le Thi Anh
authors.initials: le TA
authors.lastname: Thu
authors.forename: Hoang Lan
authors.initials: HL
authors.lastname: Phuong
authors.forename: Nguyen Canh
authors.initials: NC
authors.lastname: Hung
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000285:Administration, Rectal; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D037621:Artemisinins; D000077332:Artesunate; D016001:Confidence Intervals; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018709:Statistics, Nonparametric
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol