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Title: Population pharmacokinetic and pharmacodynamic properties of intramuscular quinine in tanzanian children with severe falciparum malaria
Authors: Ilse C E Hendriksen
Deogratius Maig
Martha M. Lemnge
George Mtove
Samwel Gesas
Hugh Reyburn
Niklas Lindegardh
Nicholas P J Day
Lorenz Von Seidlein
Arjen M. Dondorp
Joel Tarning
Nicholas J. White
Mahidol University
University of Oxford
National Institute for Medical Research Tanga
London School of Hygiene & Tropical Medicine
Menzies School of Health Research
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Feb-2013
Citation: Antimicrobial Agents and Chemotherapy. Vol.57, No.2 (2013), 775-783
Abstract: Although artesunate is clearly superior, parenteral quinine is still used widely for the treatment of severe malaria.A loading-dose regimen has been recommended for 30 years but is still often not used.A population pharmacokinetic study was conducted with 75 Tanzanian children aged 4 months to 8 years with severe malaria who received quinine intramuscularly; 69 patients received a loading dose of 20 mg quinine dihydrochloride (salt)/kg of body weight.Twenty-one patients had plasma quinine concentrations detectable at baseline.A zero-order absorption model with one-compartment disposition pharmacokinetics described the data adequately.Body weight was the only significant covariate and was implemented as an allometric function on clearance and volume parameters.Population pharmacokinetic parameter estimates (and percent relative standard errors [%RSE]) of elimination clearance, central volume of distribution, and duration of zero-order absorption were 0.977 liters/h (6.50%), 16.7 liters (6.39%), and 1.42 h (21.5%), respectively, for a typical patient weighing 11 kg.Quinine exposure was reduced at lower body weights after standard weight-based dosing; there was 18% less exposure over 24 h in patients weighing 5 kg than in those weighing 25 kg.Maximum plasma concentrations after the loading dose were unaffected by body weight.There was no evidence of dose-related drug toxicity with the loading dosing regimen.Intramuscular quinine is rapidly and reliably absorbed in children with severe falciparum malaria.Based on these pharmacokinetic data, a loading dose of 20 mg salt/kg is recommended, provided that no loading dose was administered within 24 h and no routine dose was administered within 12 h of admission.(This study has been registered with Current Controlled Trials under registration number ISRCTN 50258054.).Copyright © 2013, American Society for Microbiology.All Rights Reserved.
ISSN: 10986596
Appears in Collections:Scopus 2011-2015

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