Publication: Pharmacokinetics of mefloquine alone or in combination with artesunate
Issued Date
1994-03-25
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ISSN
00429686
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2-s2.0-0028345515
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Mahidol University
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SCOPUS
Bibliographic Citation
Bulletin of the World Health Organization. Vol.72, No.1 (1994), 83-87
Suggested Citation
J. Karbwang, K. Na Bangchang, A. Thanavibul, D. J. Back, D. Bunnag, T. Harinasuta Pharmacokinetics of mefloquine alone or in combination with artesunate. Bulletin of the World Health Organization. Vol.72, No.1 (1994), 83-87. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/9700
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Title
Pharmacokinetics of mefloquine alone or in combination with artesunate
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Abstract
A randomized comparative trial of the pharmacokinetics and pharmacodynamics of oral doses of mefloquine and of mefloquine in combination with artesunate was carried out on 20 Thai male patients with acute, uncomplicated falciparum malaria. The patients were randomized to receive either mefloquine alone (8 patients; 1250 mg of mefloquine-initial dose, 750 mg; followed 6 hours later by 500 mg), or in combination with oral artesunate (12 patients - initial dose, 200 mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12 hours later, respectively). The patients who received mefloquine alone all showed initially good responses to the treatment, with mean ± SD values for the fever clearance time (FCT) and parasite clearance time (PCT) of 44.7 ± 43.1 hours and 82.3 ± 52.3 hours, respectively. Two patients had recrudescences on day 20 and day 31 (RI response). The cure rate was 75%, and one patient had Plasmodium vivax in his peripheral blood on day 52. The patients who received the combination treatment were clinically markedly improved, with a relatively shorter FCT (31.2 ± 12.4 hours) and significantly shorter PCT (47.5 ± 19.6 hours). Four had recrudescences on days 12, 18, 26 and 33; the cure rate was 66%. Artesunate caused three significant changes in mefloquine pharmacokinetics: a decrease in the maximum concentration (C(max): 1623 ng.ml -1 versus 2212 ng.ml -1 ); an increase in the clearance rate (Cl/f: 2.9 ml.min -1 .kg -1 versus 1.1 ml.min -1 .kg -1 ); and an expansion of the volume of distribution (Vd(z)/f: 31.8 l.kg -1 versus 25.0 l.kg -1 ).