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. 1985 Nov;20(5):469–474. doi: 10.1111/j.1365-2125.1985.tb05099.x

The pharmacokinetics of mefloquine in man: lack of effect of mefloquine on antipyrine metabolism.

J H Rivière, D J Back, A M Breckenridge, R E Howells
PMCID: PMC1400721  PMID: 3878153

Abstract

A method is described for the determination of the new antimalarial agent, mefloquine, in plasma and urine. After oral administration of 750 mg mefloquine to six volunteers, absorption, was apparently slow, with plasma mefloquine concentrations at 24 h (559 +/- 181 ng ml-1; mean +/- s.d.) higher than at 6 h (459 +/- 166 ng ml-1). The elimination half-life was 373 +/- 249 h, oral clearance was 5.09 +/- 2.7 1 h-1, and apparent volume of distribution was 35.7 +/- 30.7 l kg-1 (assuming 100% bioavailability). Mefloquine (750 mg) had no significant effect on salivary kinetics of antipyrine or on the metabolic clearance of antipyrine to its three main metabolites, 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine, when antipyrine was administered either 2 h or 2 weeks after dosing with mefloquine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Back D. J., Purba H. S., Park B. K., Ward S. A., Orme M. L. Effect of chloroquine and primaquine on antipyrine metabolism. Br J Clin Pharmacol. 1983 Nov;16(5):497–502. doi: 10.1111/j.1365-2125.1983.tb02206.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Back D. J., Purba H. S., Staiger C., Orme M. L., Breckenridge A. M. Inhibition of drug metabolism by the antimalarial drugs chloroquine and primaquine in the rat. Biochem Pharmacol. 1983 Jan 15;32(2):257–263. doi: 10.1016/0006-2952(83)90553-1. [DOI] [PubMed] [Google Scholar]
  3. Danhof M., Groot-van der Vis E., Breiner D. D. Assay of antipyrine and its primary metabolites in plasma, saliva and urine by high-performance liquid chromatography and some preliminary results in man. Pharmacology. 1979;18(4):210–223. doi: 10.1159/000137254. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Grindel J. M., Tilton P. F., Shaffer R. D. Quantitation of the antimalarial agent, mefloquine, in blood, plasma, and urine using high-pressure liquid chromatography. J Pharm Sci. 1977 Jun;66(6):834–837. doi: 10.1002/jps.2600660625. [DOI] [PubMed] [Google Scholar]
  6. Kapetanovic I. M., DiGiovanni J. D., Bartosevich J., Melendez V., Von Bredow J., Heiffer M. Analysis of the antimalarial, mefloquine, in blood and plasma using high-performance liquid chromatography. J Chromatogr. 1983 Oct 14;277:209–215. doi: 10.1016/s0378-4347(00)84838-0. [DOI] [PubMed] [Google Scholar]
  7. Mendenhall D. W., Higuchi T., Sternson L. A. Analysis of hydrophobic amine antimalarials in biological fluids with the plastic ion-selective electrode. J Pharm Sci. 1979 Jun;68(6):746–750. doi: 10.1002/jps.2600680625. [DOI] [PubMed] [Google Scholar]
  8. Mihaly G. W., Ward S. A., Edwards G., Orme M. L., Breckenridge A. M. Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. Br J Clin Pharmacol. 1984 Apr;17(4):441–446. doi: 10.1111/j.1365-2125.1984.tb02369.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mu J. Y., Israili Z. H., Dayton P. G. Studies of the disposition and metabolism of mefloquine HCl (WR 142,490), a quinolinemethanol antimalarial, in the rat. Limited studies with an analog, WR 30,090. Drug Metab Dispos. 1975 May-Jun;3(3):198–210. [PubMed] [Google Scholar]
  10. Murray M. In vitro effects of quinoline derivatives on cytochrome P-450 and aminopyrine N-demethylase activity in rat hepatic microsomes. Biochem Pharmacol. 1984 Oct 15;33(20):3277–3281. doi: 10.1016/0006-2952(84)90090-x. [DOI] [PubMed] [Google Scholar]
  11. Nakagawa T., Higuchi T., Haslam J. L., Shaffer R. D., Mendenhall D. W. GLC determination of whole blood antimalarial concentrations. J Pharm Sci. 1979 Jun;68(6):718–721. doi: 10.1002/jps.2600680617. [DOI] [PubMed] [Google Scholar]
  12. Riviere J. H., Back D. J. Effect of mefloquine on hepatic drug metabolism in the rat: comparative study with primaquine. Biochem Pharmacol. 1985 Feb 15;34(4):567–571. doi: 10.1016/0006-2952(85)90191-1. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]

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