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Title: Pharmacokinetics of mefloquine combined with artesunate in children with acute falciparum malaria
Authors: Ric Price
Julie A. Simpson
Paktiya Teja-Isavatharm
Myint Myint Than
Christine Luxemburger
D. Gray Heppner
Tan Chongsuphajaisiddhi
François Nosten
Nicholas J. White
Shoklo Malaria Research Unit
St George's University of London
John Radcliffe Hospital
Mahidol University
Armed Forces Research Institute of Medical Sciences, Thailand
Walter Reed Army Institute of Research
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Feb-1999
Citation: Antimicrobial Agents and Chemotherapy. Vol.43, No.2 (1999), 341-346
Abstract: Combining artemisinin or a derivative with mefloquine increases cure rates in falciparum malaria patients, reduces transmission, and may slow the development of resistance. The combination of artesunate, given for 3 days, and mefloquine is now the treatment of choice for uncomplicated multidrug- resistant falciparum malaria acquired on the western or eastern borders of Thailand. To optimize mefloquine administration in this combination, a prospective study of mefloquine pharmacokinetics was conducted with 120 children (4 to 15 years old) with acute uncomplicated falciparum malaria, who were divided into four age- and sex-matched groups. The patients all received artesunate (4 mg/kg of body weight/day orally for 3 days and mefloquine as either (i) a single dose (25 mg/kg) on day 2 with food, (ii) a split dose (15 mg/kg on day 2 and 10 mg/kg on day 3) with food, (iii) a single dose (25 mg/kg) on day 0 without food, or (iv) a single dose (25 mg/kg) on day 2 without food. Delaying administration of mefloquine until day 2 was associated with a mean (95% confidence interval) increase in estimated oral bioavailability of 72% (36 to 109%). On day 2 coadministration with food did not increase mefloquine absorption significantly, and there were no significant differences between patients receiving split- and single-dose administration. In combination with artesunate, mefloquine administration should be delayed until the second or third day after presentation.
ISSN: 00664804
Appears in Collections:Scopus 1991-2000

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