Efficacy and Tolerance of Extended-Dose Halofantrine for Drug-Resistant Falciparum Malaria in Thailand

George Watt Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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Lersan Loesuttiviboon Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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Krisada Jongsakul Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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G. Dennis Shanks Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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Colin K. Ohrt Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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Chitraporn Karnasuta Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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Brian Schuster Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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Lawrence Fleckenstein Department of Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Surasinghanat Royal Thai Army Hospital, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, College of Pharmacy, University of Iowa, Bangkok, Thailand

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DOI:
https://doi.org/10.4269/ajtmh.1994.50.187
Volume/Issue:
Volume 50: Issue 2
Page(s):
187–192
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New treatments for malaria are urgently needed in areas such as Thailand where highly drug-resistant strains of Plasmodium falciparum are prevalent. Mefloquine is rapidly losing efficacy and conventional doses of halofantrine are ineffective. We therefore used pharmacokinetic simulation to design an extended-dose halofantrine regimen and tested it in 26 soldiers stationed along the Thai-Cambodian border. Halofantrine was given after meals as three doses of 500 mg each at 4-hr intervals on the first day, followed by 500 mg a day for six days (total dose 4.5 g). Twenty-six soldiers treated with quininetetracycline for seven days (Q7T7) served as controls. There were no significant differences in efficacy between halofantrine and Q7T7 (P > 0.1) as assessed by cure rate (92% versus 85%), mean parasite clearance time (82 hr versus 81 hr), or mean fever clearance time (93 hr versus 99 hr). Halofantrine was better tolerated than Q7T7. The side effects score was lower (2 versus 11; P < 0.001), there were less days on which side effects occurred (2.0 days versus 5.5 days; P < 0.001), and fewer patients had adverse effects on every treatment day (4% versus 42%; P < 0.01). High-dose halofantrine is as effective and better tolerated than quinine-tetracycline for multidrug-resistant falciparum malaria.
Copyright:
Copyright © 1994 by The American Society of Tropical Medicine and Hygiene 1994
Published Online:
Feb 1994
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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