Abstract
A single dose pharmacokinetic study of a combined antimalarial formulation of mefloquine, sulphadoxine and pyrimethamine (Fansimef) has been performed in 10 healthy adult male Malaysian volunteers. The dose consisted of two tablets containing 250 mg mefloquine base, 500 mg sulphadoxine base and 25 mg pyrimethamine base each. Plasma concentrations of mefloquine and pyrimethamine were measured by GC-ECD, those of sulphadoxine by h.p.l.c. Time to peak concentrations (mean +/- s.d. for mefloquine (5.70 +/- 0.95 h), sulphadoxine (3.75 +/- 2.03 h) and pyrimethamine (3.30 +/- 1.98 h) were similar to those observed by others after administration of the single compounds. This was also true for elimination half-lives (t1/2). The t1/2s for mefloquine, sulphadoxine and pyrimethamine were 387 +/- 98 h, 255 +/- 61 h and 114 +/- 42 h, respectively.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Böhni E., Fust B., Rieder J., Schaerer K., Havas L. Comparative toxicological, chemotherapeutic and pharmacokinetic studies with sulphormethoxine and other sulphonamides in animals and man. Chemotherapy. 1969;14(4):195–226. doi: 10.1159/000220630. [DOI] [PubMed] [Google Scholar]
- Cavallito J. C., Nichol C. A., Brenckman W. D., Jr, Deangelis R. L., Stickney D. R., Simmons W. S., Sigel C. W. Lipid-soluble inhibitors of dihydrofolate reductase. I. Kinetics, tissue distribution, and extent of metabolism of pyrimethamine, metoprine, and etoprine in the rat, dog, and man. Drug Metab Dispos. 1978 May-Jun;6(3):329–337. [PubMed] [Google Scholar]
- Clyde D. F., McCarthy V. C., Miller R. M., Hornick R. B. Suppressive activity of mefloquine in sporozoite-induced human malaria. Antimicrob Agents Chemother. 1976 Mar;9(3):384–386. doi: 10.1128/aac.9.3.384. [DOI] [PMC free article] [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]
- Hall A. P. The treatment of malaria. Br Med J. 1976 Feb 7;1(6005):323–328. doi: 10.1136/bmj.1.6005.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harinasuta T., Bunnag D., Vanijanond S., Charoenlarp P., Suntharasmai P., Chitamas S., Sheth U. K., Wernsdorfer W. H. Mefloquine, sulfadoxine, and pyrimethamine in the treatment of symptomatic falciparum malaria: a double-blind trial for determining the most effective dose. Bull World Health Organ. 1987;65(3):363–367. [PMC free article] [PubMed] [Google Scholar]
- Heizmann P., Geschke R. Determination of the antimalarial mefloquine in human plasma by gas chromatography with electron-capture detection. J Chromatogr. 1984 Nov 28;311(2):411–417. doi: 10.1016/s0378-4347(00)84739-8. [DOI] [PubMed] [Google Scholar]
- Jones C. R., Ovenell S. M. Determination of plasma concentrations of dapsone, monoacetyl dapsone and pyrimethamine in human subjects dosed with maloprim. J Chromatogr. 1979 Jun 11;163(2):179–185. doi: 10.1016/s0378-4347(00)81461-9. [DOI] [PubMed] [Google Scholar]
- Nosten F., Imvithaya S., Vincenti M., Delmas G., Lebihan G., Hausler B., White N. Malaria on the Thai-Burmese border: treatment of 5192 patients with mefloquine-sulfadoxine-pyrimethamine. Bull World Health Organ. 1987;65(6):891–896. [PMC free article] [PubMed] [Google Scholar]
- Pearlman E. J., Doberstyn E. B., Sudsok S., Thiemanun W., Kennedy R. S., Canfield C. J. Chemosuppressive field trials in Thailand. IV. The suppression of Plasmodium falciparum and Plasmodium vivax parasitemias by mefloquine (WR 142,490, A 4-quinolinemethanol). Am J Trop Med Hyg. 1980 Nov;29(6):1131–1137. [PubMed] [Google Scholar]
- Peck C. C., Lewis A. N., Joyce B. E. Pharmacokinetic rationale for a malarial suppressant administered once monthly. Ann Trop Med Parasitol. 1975 Jun;69(2):141–145. doi: 10.1080/00034983.1975.11686995. [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]
- 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]
- Schwartz D. E., Weber W., Richard-Lenoble D., Gentilini M. Kinetic studies of mefloquine and of one of its metabolites, Ro 21-5104, in the dog and in man. Acta Trop. 1980 Sep;37(3):238–242. [PubMed] [Google Scholar]
- Tin F., Hlaing N. Resistance to antimalarials by Plasmodium falciparum in Burma. Southeast Asian J Trop Med Public Health. 1977 Mar;8(1):104–112. [PubMed] [Google Scholar]
- Trenholme C. M., Williams R. L., Desjardins R. E., Frischer H., Carson P. E., Rieckmann K. H., Canfield C. J. Mefloquine (WR 142,490) in the treatment of human malaria. Science. 1975 Nov 21;190(4216):792–794. doi: 10.1126/science.1105787. [DOI] [PubMed] [Google Scholar]
- Weidekamm E., Schwartz D. E., Dubach U. C., Weber B. Single-dose investigation of possible interactions between the components of the antimalarial combination Fansimef. Chemotherapy. 1987;33(4):259–265. doi: 10.1159/000238505. [DOI] [PubMed] [Google Scholar]
- de Souza J. M., Sheth U. K., Wernsdorfer W. H., Trigg P. I., Doberstyn E. B. A phase II/III double-blind, dose-finding clinical trial of a combination of mefloquine, sulfadoxine, and pyrimethamine (Fansimef) in falciparum malaria. Bull World Health Organ. 1987;65(3):357–361. [PMC free article] [PubMed] [Google Scholar]