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.
Division of Infectious Diseases, Tropical Medicine & AIDS, and Department of Clinical Epidemiology and Biostatistics, Academic Medical Center Amsterdam, The Netherlands. lequochung@saigonnet.vn
Le Q
le Q
Hung
Peter J
PJ
de Vries
Tran Q
TQ
Binh
Phan T
PT
Giao
Nguyen V
NV
Nam
R
R
Holman
Piet A
PA
Kager
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077332:Artesunate; D002648:Child; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D014744:Vietnam
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; D015767:Mefloquine