title: Artemisinin population pharmacokinetics in children and adults with uncomplicated falciparum malaria.
abstract: OBJECTIVE
  To investigate the pharmacokinetics of the antimalarial artemisinin in the field setting using sparsely collected data.
  
  
  METHODS
  Artemisinin concentrations were determined by h.p.l.c. in a total of 107 capillary plasma samples collected on the first day and in 33 samples on the last day of a 5-day oral artemisinin regimen of 10 mg kg(-1) day(-1) in 23 paediatric (aged 2-12 years) and 31 adult (aged 16-45 years) Vietnamese patients with uncomplicated falciparum malaria. The population model was developed using NONMEM, incorporating interoccasion variability and accounting for a systematic change in artemisinin pharmacokinetics with time, modelled as a change in oral bioavailability.
  
  
  RESULTS
  Clinical efficacy, in terms of parasite clearance and fever subsidence times, was comparable between children and adults. A one-compartment model with separate pharmacokinetic estimates for children and adults was found best to describe the disposition of artemisinin after oral administration. The population estimates for artemisinin clearance and distribution volume, respectively, were 432 1 h(-1) and 16001 for adults and 14.41 h(-1) kg(-1) and 37.91 kg(-1) for children, with an intersubject variability (collectively for both age groups) of 45% and 104%, respectively. The oral bioavailability was estimated to decrease from Day 1 to Day 5 by a factor of 6.9, a value found to be similar for children and adults.
  
  
  CONCLUSIONS
  Artemisinin pharmacokinetic data was successfully derived in both paediatric and adult patients using 2-3 capillary blood samples taken in conjunction with parasitaemia monitoring. This study's findings advocated the dosing of artemisinin to children according to bodyweight and to adults according to a standard dose.
authors.affiliation: Division of Biopharmaceutics and Pharmacokinetics, Uppsala University, Sweden.
authors.forename: J S
authors.initials: JS
authors.lastname: Sidhu
authors.forename: M
authors.initials: M
authors.lastname: Ashton
authors.forename: N V
authors.initials: NV
authors.lastname: Huong
authors.forename: T N
authors.initials: TN
authors.lastname: Hai
authors.forename: M O
authors.initials: MO
authors.lastname: Karlsson
authors.forename: N D
authors.initials: ND
authors.lastname: Sy
authors.forename: E N
authors.initials: EN
authors.lastname: Jonsson
authors.forename: L D
authors.initials: LD
authors.lastname: Cong
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D037621:Artemisinins; D002648:Child; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin