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Population pharmaco...
Population pharmacokinetics of amodiaquine and desethylamodiaquine in pediatric patients with uncomplicated falciparum malaria
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- Friberg Hietala, Sofia, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Bhattarai, Achuyt (author)
- Karolinska Institutet
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Msellem, Mwinyi (author)
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- Röshammar, Daniel, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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Ali, Abdullah S. (author)
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Strömberg, Johan (author)
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Hombhanje, Francis W. (author)
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- Kaneko, Akira (author)
- Karolinska Institutet
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- Björkman, Anders (author)
- Karolinska Institutet
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- Ashton, Michael, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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(creator_code:org_t)
- 2007-07-10
- 2007
- English.
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In: JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 12, s. 222-222
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https://doi.org/10.1...
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Abstract
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- 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 (1/2lambda) 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- plasmodium-falciparum
- in-vitro
- disposition
- combination
- metabolite
- children
- regimens
- nonmem
- farmakokinetik malaria
Publication and Content Type
- ref (subject category)
- art (subject category)
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Friberg Hietala, ...
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Bhattarai, Achuy ...
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Msellem, Mwinyi
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Röshammar, Danie ...
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Ali, Abdullah S.
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Strömberg, Johan
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Hombhanje, Franc ...
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Kaneko, Akira
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Björkman, Anders
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Ashton, Michael, ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
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MEDICAL AND HEAL ...
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University of Gothenburg
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Karolinska Institutet