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Antimicrobial Agents and Chemotherapy, February 1999, p. 341-346, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pharmacokinetics of Mefloquine Combined with Artesunate in Children with Acute Falciparum Malaria

Ric Price,1,2,3 Julie A. Simpson,3,4 Paktiya Teja-Isavatharm,5 Myint Myint Than,1 Christine Luxemburger,1,4 D. Gray Heppner,5,dagger Tan Chongsuphajaisiddhi,4 François Nosten,1,3,4 and Nicholas J. White3,4,*

Shoklo Malaria Research Unit, Mae Sod, Tak Province,1 and Faculty of Tropical Medicine, Mahidol University,4 and Department of Immunology and Medicine, AFRIMS,5 Bangkok, Thailand, and Division of Infectious Diseases, St. George's Hospital Medical School, London,2 and Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford,3 United Kingdom

Received 22 April 1998/Returned for modification 26 August 1998/Accepted 22 November 1998

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.

* Corresponding author. Mailing address: Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. Phone: (66 2) 246 0832. Fax: (66 2) 246 7795. E-mail: fnnjw{at}diamond.mahidol.ac.th.

dagger Present address: Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, DC 20307.

Antimicrobial Agents and Chemotherapy, February 1999, p. 341-346, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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