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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Population pharmacokinetics of amodiaquine and desethylamodiaquine in pediatric patients with uncomplicated falciparum malaria
Journal of Pharmacokinetics and Pharmacodynamics, Volume 34, No. 5, Year 2007
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Description
The study aimed to characterize the population pharmacokinetics of amodiaquine (AQ) and its major metabolite N-desethylamodiaquine (N-DEAQ), and to assess the correlation between exposure to N-DEAQ and treatment outcome. Blood samples from children in two studies in Zanzibar and one in Papua New Guinea were included in the pharmacokinetic analysis (n = 86). The children had been treated with AQ in combination with artesunate or sulphadoxine-pyrimethamine. The population pharmacokinetics of AQ and N-DEAQ were modeled using the non-linear mixed effects approach as implemented in NONMEM. Bayesian post-hoc estimates of individual pharmacokinetic parameters were used to generate individual profiles of N-DEAQ exposure. The correlation between N-DEAQ exposure and effect was studied in 212 patients and modeled with logistic regression in NONMEM. The pharmacokinetics of AQ and N-DEAQ were best described by two parallel two-compartment models with a central and a peripheral compartment for each compound. The systemic exposure to AQ was low in comparison to N-DEAQ. The t 1/2λ of N-DEAQ ranged from 3 days to 12 days. There was a statistically significant, yet weak, association between N-DEAQ concentration on day 7 and treatment outcome. The age-based dosing schedule currently recommended in Zanzibar appeared to result in inadequate exposure to N-DEAQ in many patients. © 2007 Springer Science+Business Media, LLC.
Authors & Co-Authors
Hietala, Sofia Friberg
Sweden, Gothenburg
Sahlgrenska Akademin
Bhattarai, Achuyt
Sweden, Stockholm
Karolinska Universitetssjukhuset
Msellem, Mwinyi I.
Tanzania, Mkokotoni, Zanzibar
Zanzibar Malaria Elimination Programme
Röshammar, Daniel
Sweden, Gothenburg
Sahlgrenska Akademin
Ali, Abdullah Suleiman
Tanzania, Mkokotoni, Zanzibar
Zanzibar Malaria Elimination Programme
Strömberg, Johan
Sweden, Stockholm
Karolinska Universitetssjukhuset
Hombhanje, Francis Wanak
Papua new Guinea, Madang
Divine Word University
Kaneko, Akira
Sweden, Stockholm
Karolinska Universitetssjukhuset
Japan, Tokyo
Tokyo Women's Medical University
Bjǒrkman, Anders B.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Ashton, Michael
Sweden, Gothenburg
Sahlgrenska Akademin
Statistics
Citations: 49
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1007/s10928-007-9064-2
ISSN:
1567567X
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Study Locations
Guinea