1921
Volume 89, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The investigation of gender-specific partitioning of the antimalarial drug mefloquine to cellular and fluid blood compartments was performed using blood collected from a female and male healthy subject that were infected with PCM2 clone and spiked with mefloquine (0.25, 1, and 5 μM). Mefloquine concentrations in red cells of both female and male subjects were significantly higher than plasma, which suggests an intensive uptake by red cells. This was supported by a high ratio of mefloquine concentrations in the parasitized and non-parasitized red cells of about 4-fold. Gender-specific partitioning of mefloquine in parasitized blood was seen only in plasma where significantly higher concentrations were observed in female compared with male plasma. Down-adjusting the therapeutic dose of mefloquine in female patients with malaria is not advisable because mefloquine concentrations in the target cellular compartment are similar in both genders.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.13-0328
2013-10-09
2018-12-13
Loading full text...

Full text loading...

/deliver/fulltext/14761645/89/4/737.html?itemId=/content/journals/10.4269/ajtmh.13-0328&mimeType=html&fmt=ahah

References

  1. World Health Organization (WHO), 2011. World Malaria Report. Geneva: World Health Organization. [Google Scholar]
  2. World Health Organization (WHO), 2010. Guidelines for the Treatment of Malaria. Second edition. Geneva: World Health Organization. [Google Scholar]
  3. Congpuong K, Bualombai P, Banmairuroi V, Na-Bangchang K, , 2010. Compliance with a three-day course of artesunate-mefloquine combination and baseline anti-malarial treatment in an area of Thailand with highly multidrug resistant falciparum malaria. Malar J 9: 43.[Crossref] [Google Scholar]
  4. Karbwang J, White NJ, , 1990. Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet 19: 264279.[Crossref] [Google Scholar]
  5. Stürchler D, Handschin J, Kaiser D, Kerr L, Mittelholzer ML, Reber R, Fernex M, , 1991. Neuropsychiatric side effects of mefloquine. N Engl J Med 322: 17521753. [Google Scholar]
  6. Phillips-Howard P, ter Kuile F, , 1995. CNS adverse events associated with antimalarial agents. Drug Saf 12: 370383.[Crossref] [Google Scholar]
  7. Barrett PJ, Emmins PD, Clarke PD, Bradley DJ, , 1996. Comparison of adverse effects associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travelers. BMJ 313: 525528.[Crossref] [Google Scholar]
  8. Croft A, World M, , 1996. Neuropsychiatric reactions with mefloquine chemoprophylaxis. Lancet 347: 326335.[Crossref] [Google Scholar]
  9. van Riemsdijk MM, van der Klauw MM, van Heest JA, Reedeker FR, Ligthelm RJ, Herings RM, Stricker BH, , 1997. Neuro-psychiatric effects of anti-malarials. Eur J Clin Pharmacol 52: 16.[Crossref] [Google Scholar]
  10. Rønn AM, Ronne-Rasmussen J, Gotzsche PC, Bygbjerg IC, , 1998. Neuropsychiatric manifestations after mefloquine therapy for Plasmodium falciparum malaria: comparing a retrospective and a prospective study. Trop Med Int Health 3: 8388.[Crossref] [Google Scholar]
  11. Lim LY, Go ML, , 1985. The anticholinesterase activity of mefloquine. Clin Exp Pharmacol Physiol 12: 527531.[Crossref] [Google Scholar]
  12. Schwartz E, Potasman I, Rotenberg M, Almog S, Sadetzki S, , 2001. Serious adverse events of mefloquine in relation to blood level and gender. Am J Trop Med Hyg 65: 189192. [Google Scholar]
  13. Hennequin C, Bourée P, Bazin N, Bisaro F, Feline A, , 1994. Severe psychiatric side effects observed during prophylaxis and treatment with mefloquine. Arch Intern Med 154: 23602362.[Crossref] [Google Scholar]
  14. Jasper CA, Hopperus Buma AP, van Thiel PP, van Hulst RA, Kager PA, , 1996. Tolerance of mefloquine chemoprophylaxis in Dutch military tolerance personnel. Am J Trop Med Hyg 55: 230234. [Google Scholar]
  15. Schlagenhauf P, Steffen R, Lobel H, Johnson R, Letz R, Tschopp A, Vranjes N, Bergqvist Y, Ericsson O, Hellgren U, Rombo L, Mannino S, Handschin J, Stürchler D, , 1996. Mefloquine tolerability during chemoprophylaxis: focus on adverse event assessment, stereochemistry and compliance. Trop Med Int Health 1: 485494.[Crossref] [Google Scholar]
  16. Phillip M, , 1996. Adverse events associated with mefloquine: women may be more susceptible to adverse events. BMJ 313: 15521553.[Crossref] [Google Scholar]
  17. Kollaritsch H, Karbwang J, Wiedermann G, Mikolasek A, Na-Bangchang K, Wernsdorfer WH, , 2000. Mefloquine concentration profiles during prophylactic dose regimens. Wien Klin Wochenschr 112: 441447. [Google Scholar]
  18. Rendi-Wagner P, Noedl H, Wernsdorfer WH, Wiedermann G, Mikolasek A, Kollaritsch H, , 2002. Unexpected frequency, duration, and spectrum of adverse events after therapeutic dose of mefloquine in healthy adults. Acta Trop 8: 167173.[Crossref] [Google Scholar]
  19. Foley M, Tilley L, , 1998. Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. Pharmacol Ther 79: 5587.[Crossref] [Google Scholar]
  20. Trager W, Jensen JB, , 1976. Human malaria parasites in continuous culture. Science 193: 673675.[Crossref] [Google Scholar]
  21. Lambros C, Vanderberg JP, , 1979. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol 65: 418420.[Crossref] [Google Scholar]
  22. Karbwang J, Molunto P, Na Bangchang K, Bunnag D, , 1989. Determination of mefloquine in biological fluids using high performance liquid chromatography. Southeast Asian J Trop Med Public Health 20: 5560. [Google Scholar]
  23. Na-Bangchang K, Ruengweerayut R, Wernsdorfer WH, , 2011. Distribution of mefloquine in the blood of Thai patients with acute uncomplicated falciparum malaria following administration of therapeutic doses of artesunate. Eur J Clin Pharmacol 67: 687691.[Crossref] [Google Scholar]
  24. Weidekamm E, Rüsing G, Caplain H, Sörgel F, Crevoisier C, , 1998. Lack of bioequivalence of a generic mefloquine tablet with the standard product. Eur J Clin Pharmacol 54: 615619.[Crossref] [Google Scholar]
  25. Na-Bangchang K, Karbwang J, Palacios PA, Ubalee R, Saengtertsilapachai S, Wernsdorfer WH, , 2000. Pharmacokinetics and bioequivalence evaluation of three commercial tablet formulations of mefloquine when given in combination with dihydroartemisinin in patients with acute uncomplicated falciparum malaria. Eur J Clin Pharmacol 55: 743748.[Crossref] [Google Scholar]
  26. Palmer KJ, Holliday SM, Brogden RN, , 1993. Mefloquine a review of its antimalarial activity. Drug 45: 430475.[Crossref] [Google Scholar]
  27. Karbwang J, Back DJ, Bunnag D, Breckenridge AM, , 1988. A comparison of the pharmacokinetics of mefloquine in healthy Thai volunteers and in Thai patients with falciparum malaria. Eur J Clin Pharmacol 35: 677680.[Crossref] [Google Scholar]
  28. Fitch CD, Chan RL, Chevli R, , 1979. Chloroquine resistance in malaria: accessibility of drug receptors to mefloquine. Antimicrob Agents Chemother 15: 248262.[Crossref] [Google Scholar]
  29. San George RC, Nagel RL, Farby ME, , 1984. On the mechanism of the red-cell accumulation of mefloquine, and antimalarial drug. Biochim Biophys Acta 803: 174181.[Crossref] [Google Scholar]
  30. Chevil R, Fitch CD, , 1992. The antimalarial drug mefloquine binds to membrane phospholipids. Antimicrob Agents Chemother 21: 581586.[Crossref] [Google Scholar]
  31. Weinke T, Trautmann M, Held T, Weber G, Eichenlaub D, Fleischer K, Kern W, Pohle HD, , 1991. Neuropsychiatric side effects after the use of mefloquine. Am J Trop Med Hyg 45: 8691. [Google Scholar]
  32. McIntosh HM, Olliaro P, , 2006. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database Syst Rev 2. [Google Scholar]
  33. ter Kuile FC, Luxemburger F, Nosten L, Phaipun T, Chongsuphajaisiddhi T, White NJ, , 1995. Predictors of mefloquine treatment failure: a prospective study in 1590 patients with uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 89: 660664.[Crossref] [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.13-0328
Loading
/content/journals/10.4269/ajtmh.13-0328
Loading

Data & Media loading...

  • Received : 05 Jun 2013
  • Accepted : 27 Jul 2013

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error