Studies on the Chemotherapy of the Human Malarias. Ii. Method for the Quantitative Assay of Suppressive Antimalarial Action in Falciparum Malaria 123

f 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.)

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“…Plasma concentrations of up to 20 mg/liter have not been associated with significant toxicity in severe malaria (11,(39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic and Pharmacodynamic Properties of Intramuscular Quinine in Tanzanian Children with Severe Falciparum Malaria

Hendriksen

Maiga

Lemnge

et al. 2013

Antimicrob Agents Chemother

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“…The therapeutic tests with blood-induced malaria were performed in accordance with standard procedures outlined in the preceding papers (5,6). Therapy was started on the fourth day after the onset of fever in vivax malaria and on the first or second day of fever in falciparum malaria.…”

Section: Methodsmentioning

confidence: 99%

Studies on the Chemotherapy of the Human Malarias. Iii. The Physiological Disposition and Antimalarial Activity of the Cinchona Alkaloids 123

Taggart

Earle²,

Berliner³

et al. 1948

J. Clin. Invest.

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“…Data of this type, on each of the 4-aminoquinolines studied, are summarized in Table V The values for activity obtained in these studies are not considered to be directly applicable to all strains of plasmodia. However, the tests in bloodinduced infections utilized strains of P. zivax (McCoy) and P. falciparum (McClendon) whose susceptibility to quinine and quinacrine is known (12,13,14). The testing procedures have been demonstrated to yield reproducible results which define the chemotherapeutic susceptibilities of various strains.…”

Section: Section I Physiological Dispositionmentioning

confidence: 99%

“…All of the therapeutic tests with bloodinduced malaria were performed in accordance with standard procedures previously outlined (12,13). The regimens of dosage were designed to produce fairly stable plasma drug concentrations during the four-day (vivax) or six-day (falciparum) therapeutic period as in the quinacrine studies (14).…”

Section: Section I Physiological Dispositionmentioning

confidence: 99%

Studies on the Chemotherapy of the Human Malarias. Vi. The Physiological Disposition, Antimalarial Activity, and Toxicity of Several Derivatives of 4-Aminoquinoline 12

Berliner¹,

Earle²,

Taggart³

et al. 1948

J. Clin. Invest.

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169

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Studies on the Chemotherapy of the Human Malarias. Ii. Method for the Quantitative Assay of Suppressive Antimalarial Action in Falciparum Malaria 123

Cited by 19 publications

References 2 publications

Population Pharmacokinetic and Pharmacodynamic Properties of Intramuscular Quinine in Tanzanian Children with Severe Falciparum Malaria

Population Pharmacokinetic and Pharmacodynamic Properties of Intramuscular Quinine in Tanzanian Children with Severe Falciparum Malaria

Studies on the Chemotherapy of the Human Malarias. Iii. The Physiological Disposition and Antimalarial Activity of the Cinchona Alkaloids 123

Studies on the Chemotherapy of the Human Malarias. Vi. The Physiological Disposition, Antimalarial Activity, and Toxicity of Several Derivatives of 4-Aminoquinoline 12

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