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Population Pharmaco...
Population Pharmacokinetics of Artemether, Dihydroartemisinin, and Lumefantrine in Rwandese Pregnant Women Treated for Uncomplicated Plasmodium falciparum Malaria
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- Lohy Das, Jesmin, 1979- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Rulisa, Stephen (författare)
- Univ Kigali, Dept Clin Res, Kigali, Rwanda
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- de Vries, Peter J. (författare)
- Tergooi Hosp, Hilversum, Netherlands
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- Mens, Petra F. (författare)
- Acad Med Ctr, Dept Med Microbiol, Amsterdam, Netherlands
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- Kaligirwa, Nadine (författare)
- Rwanda Biomed Ctr, Ctr Treatment & Res AIDS Malaria & TB TRAC PLUS, Kigali, Rwanda
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- Agaba, Steven (författare)
- Rwanda Biomed Ctr, Ctr Treatment & Res AIDS Malaria & TB TRAC PLUS, Kigali, Rwanda
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- Tarning, Joel (författare)
- Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England;Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand
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- Karlsson, Mats O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Dorlo, Thomas P. C. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Pharm & Pharmacol, Amsterdam, Netherlands
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(creator_code:org_t)
- AMER SOC MICROBIOLOGY, 2018
- 2018
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 62:10
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The artemisinin-based combination therapy artemether-lumefantrine is commonly used in pregnant malaria patients. However, the effect of pregnancy-related changes on exposure is unclear, and pregnancy has been associated with decreased efficacy in previous studies. This study aimed to characterize the population pharmacokinetics of artemether, its active metabolite dihydroartemisinin, and lumefantrine in 22 Rwandese pregnant women in their second (n = 11) or third (n = 11) trimester with uncomplicated Plasmodium falciparum malaria. These patients were enrolled from Rwamagana district hospital and received the standard fixed oral dose combination of 80 mg of artemether and 480 mg of lumefantrine twice daily for 3 days. Venous plasma concentrations were quantified for all three analytes using liquid chromatography coupled with tandem mass spectroscopy, and data were analyzed using nonlinear mixed-effects modeling. Lumefantrine pharmacokinetics was described by a flexible but highly variable absorption, with a mean absorption time of 4.04 h, followed by a biphasic disposition model. The median area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) for lumefantrine was 641 h . mg/liter. Model-based simulations indicated that 11.7% of the study population did not attain the target day 7 plasma concentration (280 ng/ml), a threshold associated with increased risk of recrudescence. The pharmacokinetics of artemether was time dependent, and the autoinduction of its clearance was described using an enzyme turnover model. The turnover half-life was predicted to be 30.4 h. The typical oral clearance, which started at 467 liters/h, increased 1.43-fold at the end of treatment. Simulations suggested that lumefantrine pharmacokinetic target attainment appeared to be reassuring in Rwandese pregnant women, particularly compared to target attainment in Southeast Asia. Larger cohorts will be required to confirm this finding.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- artemether
- dihydroartemisinin
- lumefantrine
- malaria
- pharmacokinetics
- pharmacometrics
- pregnancy
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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