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ARTESUNATE WITH MEFLOQUINE AT VARIOUS INTERVALS FOR NON-SEVERE PLASMODIUM FALCIPARUM MALARIA

To study the efficacy, tolerance, population pharmacokinetics and pharmacodynamics of artesunate followed by mefloquine at various intervals, 360 patients with Plasmodium falciparum malaria received 4 mg/kg of artesunate and thereafter 15 mg/kg of mefloquine simultaneously (group A), after 8 hours (after group B), and after 24 hours (group C). Three dosages were completed with placebo. Follow-up was 28 days. All patients recovered rapidly except one case of failure within the first 24 hours. Mefloquine pharmacokinetics was similar in the three regimens. Parasites reappeared in 26%, 26%, and 33% of the patients in groups A, B, and C, respectively. Early recrudescence was associated with high initial parasite density, slow parasite clearance, and rapid mefloquine clearance and low plasma concentrations at day 28. Mefloquine plasma concentrations all reached therapeutic ranges, suggesting reduced parasite sensitivity. In conclusion, there is no interaction between artesunate and mefloquine with respect to tolerance, efficacy, and pharmacokinetics. Single-dose combination therapy with artemisinin drugs and 15 mg/kg of mefloquine does not completely prevent parasite recurrence and may not prevent mefloquine resistance.

Received September 18, 2003. Accepted for publication February 27, 2004.

Authors’ addresses: Le Q. Hung and Phan T. Giao, Division of Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center F4-217, PO Box 22700, 1100 DE Amsterdam, The Netherlands and Department of Tropical Diseases, Cho Ray Hospital, 201 B Nguyen Chi Thanh, District 5, Ho Chi Minh City, Vietnam, E-mail: lequochung{at}saigonnet.vn. Peter J. De Vries and Piet A. Kager, Division of Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center F4-217, PO Box 22700, 1100 DE Amsterdam, The Netherlands, E-mails: p.j.devries{at}amc.uva.nl and p.a.kager{at}amc.uva.nl. Tran Q. Binh, Department of Tropical Diseases, Cho Ray Hospital, 201 B Nguyen Chi Thanh, District 5, Ho Chi Minh City, Vietnam, E-mail: binhtq{at}hcm.vnn.vn. Nguyen V. Nam, Binh Thuan Provincial Malaria Center, Phan Thiet, Binh Thuan Province, Vietnam. R. Holman, Department of Clinical Epidemiology and Biostatistics, Academic Medical Center J2-212, PO Box 22700, 1100 DE Amsterdam, the Netherlands, E-mail: r.holman{at}amc.uva.nl.

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