title: A single dose of intramuscular sulfadoxine-pyrimethamine as an adjunct to quinine in the treatment of severe malaria: pharmacokinetics and efficacy.
abstract: It has been suggested that sulfadoxine-pyrimethamine (SD/PM) may be useful in the treatment of severe malaria since it could enhance the killing of parasites by quinine (QN) and it can be given as a single intramuscular injection. Eighty Kenyan children with severe malaria were allocated at random to receive either intramuscular QN alone (quinine dihydrochloride 20 mg salt/kg as a loading dose, followed by 10 mg salt/kg 12 hourly for a total of 6 doses) or the same QN regimen plus one intramuscular injection of SD/PM (sulfadoxine 25 mg/kg, pyrimethamine 1.25 mg/kg). There was no difference in time to defervescence, aparasitaemia, or 50% reduction in parasitaemia, parasite elimination half-life, or mortality between the 2 groups. In addition, the concentrations of SD and PM were measured in 14 children and of QN in 8 of these children. Concentrations needed to achieve synergy against PM-resistant strains of Plasmodium falciparum were achieved in all of the children with severe malaria within the first hour and maintained for more than 72 h. SD/PM did not perturb the pharmacokinetics of QN.
authors.affiliation: Kenya Medical Research Institute, Kilifi Research Unit, Kenya.
authors.forename: C R
authors.initials: CR
authors.lastname: Newton
authors.forename: P A
authors.initials: PA
authors.lastname: Winstanley
authors.forename: W M
authors.initials: WM
authors.lastname: Watkins
authors.forename: I N
authors.initials: IN
authors.lastname: Mwangi
authors.forename: C M
authors.initials: CM
authors.lastname: Waruiru
authors.forename: E K
authors.initials: EK
authors.lastname: Mberu
authors.forename: P A
authors.initials: PA
authors.lastname: Warn
authors.forename: C G
authors.initials: CG
authors.lastname: Nevill
authors.forename: K
authors.initials: K
authors.lastname: Marsh
mesh_terms: D000208:Acute Disease; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy*; D008297:Male; D011739:Pyrimethamine / Q000097:blood / Q000627:therapeutic use*; D011803:Quinine / Q000097:blood / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000097:blood / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D013413:Sulfadoxine; D011803:Quinine; D011739:Pyrimethamine