Publication: Mefloquine pharmacokinetic-pharmacodynamic models: Implications for dosing and resistance
Issued Date
2000-12-01
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ISSN
00664804
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2-s2.0-0034425550
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.44, No.12 (2000), 3414-3424
Suggested Citation
J. A. Simpson, E. R. Watkins, R. N. Price, L. Aarons, D. E. Kyle, N. J. White Mefloquine pharmacokinetic-pharmacodynamic models: Implications for dosing and resistance. Antimicrobial Agents and Chemotherapy. Vol.44, No.12 (2000), 3414-3424. doi:10.1128/AAC.44.12.3414-3424.2000 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/26038
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Title
Mefloquine pharmacokinetic-pharmacodynamic models: Implications for dosing and resistance
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Abstract
Antimalarial resistance develops and spreads when spontaneously occurring mutant malaria parasites are selected by concentrations of antimalarial drug which are sufficient to eradicate the more sensitive parasites but not those with the resistance mutation(s). Mefloquine, a slowly eliminated quinoline-methanol compound, is the most widely used drug for the treatment of multidrug-resistant falciparum malaria. It has been used at doses ranging between 15 and 25 mg of base/kg of body weight. Resistance to mefloquine has developed rapidly on the borders of Thailand, where the drug has been deployed since 1984. Mathematical modeling with population pharmacokinetic and in vivo and in vitro pharmacodynamic data from this region confirms that, early in the evolution of resistance, conventional assessments of the therapeutic response ≤28 days after treatment underestimate considerably the level of resistance. Longer follow-up is required. The model indicates that initial deployment of a lower (15-mg/kg) dose of mefloquine provides a greater opportunity for the selection of resistant mutants and would be expected to lead more rapidly to resistance than de novo use of the higher (25-mg/kg) dose.