Abstract
Mefloquine-sulphadoxine-pyrimethamine (MSP) in combination has proved effective against multiple-drug-resistant falciparum malaria, but nothing is known about mefloquine absorption when it is given in this formulation. Nine Thai patients, aged 15-51 years with uncomplicated chloroquine-resistant falciparum malaria, took 11.2-16.7 mg of mefloquine base per kilogram bodyweight as MSP tablets. All patients responded to treatment with fever and parasite clearance times of 61 +/- 29 h (mean +/- s.d.) and 52 +/- 24 h, respectively. The mean apparent absorption half-time (t1/2abs) of mefloquine was 4.89 h (range 2.25-9.72) and mean peak plasma concentration was 1815 ng ml-1 (range 725-3368). Peak plasma mefloquine concentrations in three patients who vomited within 2 h of treatment were 725, 956 and 1972 ng ml-1. There was no significant difference between plasma and whole blood mefloquine concentrations during the first 48 h of treatment. Based on the elimination of parasitaemia, the plasma mefloquine concentrations are adequate for therapy of uncomplicated falciparum malaria although the relationship between plasma concentrations and therapeutic efficacy of mefloquine requires further study.
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- Chanthavanich P., Looareesuwan S., White N. J., Warrell D. A., Warrell M. J., DiGiovanni J. H., von Bredow J. Intragastric mefloquine is absorbed rapidly in patients with cerebral malaria. Am J Trop Med Hyg. 1985 Nov;34(6):1028–1036. doi: 10.4269/ajtmh.1985.34.1028. [DOI] [PubMed] [Google Scholar]
- Desjardins R. E., Pamplin C. L., 3rd, von Bredow J., Barry K. G., Canfield C. J. Kinetics of a new antimalarial, mefloquine. Clin Pharmacol Ther. 1979 Sep;26(3):372–379. doi: 10.1002/cpt1979263372. [DOI] [PubMed] [Google Scholar]
- Fitch C. D., Chan R. L., Chevli R. Chloroquine resistance in malaria: accessibility of drug receptors to mefloquine. Antimicrob Agents Chemother. 1979 Feb;15(2):258–262. doi: 10.1128/aac.15.2.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harinasuta T., Bunnag D., Lasserre R., Leimer R., Vinijanont S. Trials of mefloquine in vivax and of mefloquine plus 'fansidar' in falciparum malaria. Lancet. 1985 Apr 20;1(8434):885–888. doi: 10.1016/s0140-6736(85)91670-8. [DOI] [PubMed] [Google Scholar]
- Harinasuta T., Bunnag D., Wernsdorfer W. H. A phase II clinical trial of mefloquine in patients with chloroquine-resistant falciparum malaria in Thailand. Bull World Health Organ. 1983;61(2):299–305. [PMC free article] [PubMed] [Google Scholar]
- Harinasuta T., Dixon K. E., Warrell D. A., Doberstyn E. B. Recent advances in malaria with special reference to Southeast Asia. Southeast Asian J Trop Med Public Health. 1982 Mar;13(1):1–34. [PubMed] [Google Scholar]
- Herzog C., Ellis C. J., Innes J. A., Fletcher K. A. Possible role of drug malabsorption in recrudescence of falciparum malaria. Lancet. 1982 Nov 20;2(8308):1157–1158. doi: 10.1016/s0140-6736(82)92807-0. [DOI] [PubMed] [Google Scholar]
- Meek S. R., Doberstyn E. B., Gaüzère B. A., Thanapanich C., Nordlander E., Phuphaisan S. Treatment of falciparum malaria with quinne and tetracycline or combined mefloquine/sulfadoxine/pyrimethamine on the Thai-Kampuchean border. Am J Trop Med Hyg. 1986 Mar;35(2):246–250. doi: 10.4269/ajtmh.1986.35.246. [DOI] [PubMed] [Google Scholar]
- Miller K. D., Lobel H. O., Satriale R. F., Kuritsky J. N., Stern R., Campbell C. C. Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis. Am J Trop Med Hyg. 1986 May;35(3):451–458. doi: 10.4269/ajtmh.1986.35.451. [DOI] [PubMed] [Google Scholar]
- Rivière J. H., Back D. J., Breckenridge A. M., Howells R. E. The pharmacokinetics of mefloquine in man: lack of effect of mefloquine on antipyrine metabolism. Br J Clin Pharmacol. 1985 Nov;20(5):469–474. doi: 10.1111/j.1365-2125.1985.tb05099.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- San George R. C., Nagel R. L., Fabry M. E. On the mechanism for the red-cell accumulation of mefloquine, an antimalarial drug. Biochim Biophys Acta. 1984 Mar 23;803(3):174–181. doi: 10.1016/0167-4889(84)90007-7. [DOI] [PubMed] [Google Scholar]
- Schwartz D. E., Eckert G., Hartmann D., Weber B., Richard-Lenoble D., Ekue J. M., Gentilini M. Single dose kinetics of mefloquine in man. Plasma levels of the unchanged drug and of one of its metabolites. Chemotherapy. 1982;28(1):70–84. doi: 10.1159/000238062. [DOI] [PubMed] [Google Scholar]