Publication: Pharmacokinetic and pharmacodynamic interactions of mefloquine and dihydroartemisinin
Issued Date
1999-08-12
Resource Type
ISSN
02511649
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2-s2.0-0032854190
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Mahidol University
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SCOPUS
Bibliographic Citation
International Journal of Clinical Pharmacology Research. Vol.19, No.1 (1999), 9-17
Suggested Citation
Kesara Na-Bangchang, P. Tippawangkosol, A. Thanavibul, R. Ubalee, J. Karbwang Pharmacokinetic and pharmacodynamic interactions of mefloquine and dihydroartemisinin. International Journal of Clinical Pharmacology Research. Vol.19, No.1 (1999), 9-17. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/25603
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Title
Pharmacokinetic and pharmacodynamic interactions of mefloquine and dihydroartemisinin
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Abstract
Pharmacokinetic and pharmacodynamic interactions between dihydroartemisinin and mefloquine were investigated in 10 healthy Thai males. The study was of a three-way crossover design. Subjects were randomized to receive three drug regimens on three separate occasions as follows: regimen I: a single oral dose of 300 mg dihydroartemisinin; regimen II: a single oral dose of 750 mg mefloquine, regimen III: a single oral dose of 300 mg dihydroartemisinin, given concurrently with a single oral dose of 750 mg mefloquine. All regimens were well tolerated. Oral dihydroartemisinin was rapidly absorbed and disappeared from systemic circulation within 8-10 h. Mefloquine absorption and disposition were relatively slow processes. Pharmacokinetics of dihydroartemisinin and mefloquine when given concurrently were similar except for the absorption rate of mefloquine which was faster in the presence of dihydroartemisinin. Pharmacodynamically, the combination of dihydroartemisinin and mefloquine resulted in a synergistic effect on ex vivo blood schizontocidal activity. Maximum activity (A(max)) and area under effect-time curve (AUEC) of dihydroartemisinin and mefloquine were increased approximately two- and 20-fold (A(max)), and four- and twofold respectively compared with each individual drug alone. AUEC of mefloquine during the first 24 h (AUEC(0-24h)) was increased approximately 50-fold in the presence of dihydroartemisinin.