Population Pharmacokinetics of Lumefantrine in Pregnant Women Treated with Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria
| Autor: | Mupawjay Pimanpanarak, Anna Annerberg, Benjamas Kamanikom, Pratap Singhasivanon, Nicholas P. J. Day, Kasia Stepniewska, Rose McGready, Nicholas J. White, Elizabeth A. Ashley, François Nosten, Joel Tarning, Niklas Lindegardh |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
medicine.medical_specialty Artemether/lumefantrine Adolescent Population Pharmacology Lumefantrine Antimalarials Young Adult chemistry.chemical_compound Pharmacokinetics Pregnancy medicine Animals Humans Pharmacology (medical) Artemether Malaria Falciparum education Volume of distribution Fluorenes education.field_of_study Obstetrics business.industry medicine.disease Artemisinins Logistic Models Infectious Diseases chemistry Ethanolamines Female business Malaria medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 53:3837-3846 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00195-09 |
| Popis: | Artemether-lumefantrine has become one of the most widely used antimalarial drugs in the world. The objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multidrug-resistant Plasmodium falciparum malaria on the northwestern border of Thailand. Burmese and Karen women ( n = 103) with P. falciparum malaria and in the second and third trimesters of pregnancy were treated with artemether-lumefantrine (80/480 mg) twice daily for 3 days. All patients provided five capillary plasma samples for drug quantification, and the collection times were randomly distributed over 14 days. The concentration-time profiles of lumefantrine were assessed by nonlinear mixed-effects modeling. The treatment failure rate (PCR-confirmed recrudescent infections at delivery) was high; 16.5% (95% confidence interval, 9.9 to 25.1). The population pharmacokinetics of lumefantrine were described well by a two-compartment open model with first-order absorption and elimination. The final model included interindividual variability in all pharmacokinetic parameters and a linear covariate relationship between the estimated gestational age and the central volume of distribution. A high proportion of all women (40%, 41/103) had day 7 capillary plasma concentrations of |
| Databáze: | OpenAIRE |
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