Population Pharmacokinetics of Intramuscular Quinine in Children with Severe Malaria
| Autor: | George N. Henderson, Hartmut Derendorf, Tim Planche, Nelamangala V. Nagaraja, Alex Owusu-Ofori, Tsiri Agbenyega, George Bedo-Addo, Alan D. Hutson, Albert L. Shroads, Sanjeev Krishna, Peter W. Stacpoole, Daniel Ansong |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Metabolic Clearance Rate Plasmodium falciparum Population Parasitemia Ghana Injections Intramuscular Loading dose Antimalarials Pharmacokinetics parasitic diseases Animals Humans Medicine Pharmacology (medical) Malaria Falciparum Child education Pharmacology Volume of distribution education.field_of_study Quinine Dichloroacetic Acid biology business.industry Hemodynamics Infant medicine.disease biology.organism_classification Infectious Diseases Child Preschool Anesthesia Acidosis Lactic Female business Malaria Half-Life medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 45:1803-1809 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.45.6.1803-1809.2001 |
| Popis: | 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 β 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. |
| Databáze: | OpenAIRE |
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