title: Effects of amodiaquine and artesunate on sulphadoxine-pyrimethamine pharmacokinetic parameters in children under five in Mali.
abstract: BACKGROUND
  Sulphadoxine-pyrimethamine, in combination with artesunate or amodiaquine, is recommended for the treatment of uncomplicated malaria and is being evaluated for intermittent preventive treatment. Yet, limited data is available on pharmacokinetic interactions between these drugs.
  
  
  METHODS
  In a randomized controlled trial, children aged 6-59 months with uncomplicated falciparum malaria, received either one dose of sulphadoxine-pyrimethamine alone (SP), one dose of SP plus three daily doses of amodiaquine (SP+AQ) or one dose of SP plus 3 daily doses of artesunate (SP+AS). Exactly 100 μl of capillary blood was collected onto filter paper before drug administration at day 0 and at days 1, 3, 7, 14, 21 and 28 after drug administration for analysis of sulphadoxine and pyrimethamine pharmacokinetic parameters.
  
  
  RESULTS
  Fourty, 38 and 31 patients in the SP, SP+AQ and SP+AS arms, respectively were included in this study. The concentrations on day 7 (that are associated with therapeutic efficacy) were similar between the SP, SP+AQ and SP+AS treatment arms for sulphadoxine (median [IQR] 35.25 [27.38-41.70], 34.95 [28.60-40.85] and 33.40 [24.63-44.05] μg/mL) and for pyrimethamine (56.75 [46.40-92.95], 58.75 [43.60-98.60] and 59.60 [42.45-86.63] ng/mL). There were statistically significant differences between the pyrimethamine volumes of distribution (4.65 [3.93-6.40], 4.00 [3.03-5.43] and 5.60 [4.40-7.20] L/kg; p = 0.001) and thus elimination half-life (3.26 [2.74 -3.82], 2.78 [2.24-3.65] and 4.02 [3.05-4.85] days; p < 0.001). This study confirmed the lower SP concentrations previously reported for young children when compared with adult malaria patients.
  
  
  CONCLUSIONS
  Despite slight differences in pyrimethamine volumes of distribution and elimination half-life, these data show similar exposure to SP over the critical initial seven days of treatment and support the current use of SP in combination with either AQ or AS for uncomplicated falciparum malaria treatment in young Malian children.
authors.affiliation: Molecular Epidemiology and Drug Resistance Unit, Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, P,O, Box: 1805, Bamako, Mali.
authors.forename: Mamadou M
authors.initials: MM
authors.lastname: Tekete
authors.forename: Sékou
authors.initials: S
authors.lastname: Toure
authors.forename: Alfia
authors.initials: A
authors.lastname: Fredericks
authors.forename: Abdoul H
authors.initials: AH
authors.lastname: Beavogui
authors.forename: Cheick P O
authors.initials: CP
authors.lastname: Sangare
authors.forename: Alicia
authors.initials: A
authors.lastname: Evans
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.forename: Hamma
authors.initials: H
authors.lastname: Maiga
authors.forename: Zoumana I
authors.initials: ZI
authors.lastname: Traore
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Karen I
authors.initials: KI
authors.lastname: Barnes
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimde
mesh_terms: D000655:Amodiaquine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077332:Artesunate; D001774:Blood Chemical Analysis; D002675:Child, Preschool; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy; D008297:Male; D008302:Mali; D011739:Pyrimethamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine