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Antimicrobial Agents and Chemotherapy, June 2001, p. 1803-1809, Vol. 45, No. 6
Department of Infectious Diseases, St. George's Hospital
Medical School, Cranmer Terrace, London SW17 ORE, United
Kingdom1; Department of Physiology,
University of Science and Technology, School of Medical
Sciences,3 and Departments of
Paediatrics and Medicine, Komfo-Anokye Teaching
Hospital,4 Kumasi, Ghana; Department of
Medicine (Division of Endocrinology and
Metabolism),5 Departments of
Biochemistry and Molecular Biology,7 and
Department of Statistics (Division of
Biostatistics),6 University of Florida College
of Medicine, Gainesville, Florida 32610-0226; and
Department of Pharmaceutics, University of Florida College of
Pharmacy, Gainesville, Florida 32610-04942
Received 7 September 2000/Returned for modification 10 February
2001/Accepted 13 March 2001
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 [V1] = 0.65 liter/kg;
volume of distribution at steady state = 1.41 liter/kg; half-life
at
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.6.1803-1809.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Population Pharmacokinetics of Intramuscular
Quinine in Children with Severe Malaria
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 V1. 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.
*
Corresponding author. Mailing address: Department of
Infectious Diseases, St. George's Hospital Medical School, Cranmer
Terrace, London SW17 ORE, United Kingdom. Phone: 44 20 8725 5827. Fax: 44 20 8725 3487. E-mail: s.krishna{at}sghms.ac.uk.
Antimicrobial Agents and Chemotherapy, June 2001, p. 1803-1809, Vol. 45, No. 6
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.6.1803-1809.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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