title: The safety and kinetics of intramuscular quinine in Malawian children with moderately severe falciparum malaria.
abstract: The safety and kinetics of intramuscular quinine (10 mg salt/kg every 8 h for 3 doses) were assessed in Malawian children suffering from uncomplicated falciparum malaria, who were unable to take oral antimalarial drugs. Treatment was completed with oral pyrimethamine-sulfadoxine. The mean (+/- SD) peak plasma quinine concentration after the first injection was 9.0 (+/- 2.3) micrograms/ml, at 1.1 (+/- 0.7) h. Mean plasma concentrations increased further after the second and third doses to a maximum of 11.5 (+/- 2.6) micrograms/ml at 16.1 (+/- 3.2) h. No hypotension, hypoglycaemia or electrocardiographic abnormalities developed during quinine treatment. These results provide further evidence for the safety of intramuscular quinine in children with moderately severe malaria. Plasma concentrations of alpha 1-acid glycoprotein (AGP) were higher, and the degree of protein binding of quinine was greater, in acute malaria than in convalescence. There was a significant correlation between AGP concentration and the fraction of plasma quinine bound to plasma protein. These findings suggest a role for AGP in the binding of quinine in plasma in vivo and are of interest since unbound quinine is responsible for both the efficacy and toxicity of the drug.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Mansor
authors.forename: T E
authors.initials: TE
authors.lastname: Taylor
authors.forename: C S
authors.initials: CS
authors.lastname: McGrath
authors.forename: G
authors.initials: G
authors.lastname: Edwards
authors.forename: S A
authors.initials: SA
authors.lastname: Ward
authors.forename: J J
authors.initials: JJ
authors.lastname: Wirima
authors.forename: M E
authors.initials: ME
authors.lastname: Molyneux
mesh_terms: D000818:Animals; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008288:Malaria / Q000097:blood / Q000188:drug therapy*; D008295:Malawi; D008297:Male; D009961:Orosomucoid / Q000378:metabolism; D010963:Plasmodium falciparum; D011803:Quinine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D009961:Orosomucoid; D011803:Quinine