title: Towards optimal regimens of parenteral quinine for young African children with cerebral malaria: the importance of unbound quinine concentration.
abstract: Young African children with severe malaria are given quinine using a regimen designed for Thai adults. We measured quinine in the blood, plasma and plasma water of young children in Kenya after rapid intravenous and intramuscular dosing, and calculated the therapeutic range of unbound quinine. The peak plasma quinine concentration after rapid intravenous dosing was 12.3 +/- 3.7 mg/L (mean +/- SD), 43% higher than in adults given the same regimen previously; this was due to a smaller apparent volume of distribution in the children. The therapeutic range of unbound quinine was calculated as 0.2-2.0 mg/L. Simulations of unbound quinine were made for the standard quinine regimen: unbound drug concentrations rose above the therapeutic range after each dose. The possible risks of quinine-induced visual impairment are discussed. Alternative, lower dose regimens for young African children with severe malaria are described.
authors.affiliation: Kenya Medical Research Institute, Kilifi Unit.
authors.forename: P
authors.initials: P
authors.lastname: Winstanley
authors.forename: C
authors.initials: C
authors.lastname: Newton
authors.forename: W
authors.initials: W
authors.lastname: Watkins
authors.forename: E
authors.initials: E
authors.lastname: Mberu
authors.forename: S
authors.initials: S
authors.lastname: Ward
authors.forename: P
authors.initials: P
authors.lastname: Warn
authors.forename: I
authors.initials: I
authors.lastname: Mwangi
authors.forename: C
authors.initials: C
authors.lastname: Waruiru
authors.forename: G
authors.initials: G
authors.lastname: Pasvol
authors.forename: D
authors.initials: D
authors.lastname: Warrell
mesh_terms: D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D016779:Malaria, Cerebral / Q000188:drug therapy*; D011803:Quinine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
chemical_list: D011803:Quinine