Population pharmacokinetics of intramuscular quinine in children with severe malaria.

Author(s): Krishna S, Nagaraja NV, Planche T, Agbenyega T, Bedo-Addo G, Ansong D, Owusu-Ofori A, Shroads AL, Henderson G, Hutson A, Derendorf H, Stacpoole PW

Affiliation(s): Department of Infectious Diseases, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom. s.krishna@shgms.ac.uk

Publication date & source: 2001-06, Antimicrob Agents Chemother., 45(6):1803-9.

Publication type: Clinical Trial; Randomized Controlled Trial; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.

We present the first population pharmacokinetic analysis of quinine in patients with Plasmodium falciparum malaria. Ghanaian children (n = 120; aged 12 months to 10 years) with severe malaria received an intramuscular loading dose of quinine dihydrochloride (20 mg/kg of body weight). A two-compartment model with first-order absorption and elimination gave post hoc estimates for pharmacokinetic parameters that were consistent with those derived from non-population pharmacokinetic studies (clearance [CL] = 0.05 liter/h/kg of body weight; volume of distribution in the central compartment [V(1)] = 0.65 liter/kg; volume of distribution at steady state = 1.41 liter/kg; half-life at beta phase = 19.9 h). There were no covariates (including age, gender, acidemia, anemia, coma, parasitemia, or anticonvulsant use) that explained interpatient variability in weight-normalized CL and V(1). Intramuscular quinine was associated with minor, local toxicity in some patients (13 of 108; 12%), and 11 patients (10%) experienced one or more episodes of postadmission hypoglycemia. A loading dose of intramuscular quinine results in predictable population pharmacokinetic profiles in children with severe malaria and may be preferred to the intravenous route of administration in some circumstances.