Volume 83, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted.


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  1. Croft AM, Garner P, , 2000. Mefloquine for preventing malaria in non-immune adult travellers. Review. Cochrane Database Sys Rev 4: CD000138. [Google Scholar]
  2. Giao PT, de Vries PJ, , 2001. Pharmacokinetic interactions of antimalarial agents. Clin Pharmacokinet 40: 343373.[Crossref] [Google Scholar]
  3. Baird JK, , 2005. Effectivenss of antimalarial drugs. N Engl J Med 352: 15651577.[Crossref] [Google Scholar]
  4. Karle JM, Olmeda R, Gerena L, Milhous WK, , 1993. Plasmodium falciparum: role of absolute stereochemistry in the antimalarial activity of synthetic amino alcohol antimalarial agents. Exp Parasitol 76: 345351.[Crossref] [Google Scholar]
  5. Basco LK, Gillotin C, Gimenez F, Farinotti R, Le Bras J, , 1992. In vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline against Plasmodium falciparum . Br J Clin Pharmacol 33: 517520.[Crossref] [Google Scholar]
  6. Cerebrus Ltd, 1998. Patent WO 98/39003. [Google Scholar]
  7. Ngiam TL, Go ML, , 1987. Stereospecific inhibition of cholinesterases be mefloquine enantiomers. Chem Pharm Bull (Tokyo) 35: 409412.[Crossref] [Google Scholar]
  8. Barrett P, Emmins P, Clarke PD, Bradley DJ, , 1996. Comparison of the adverse events associated with the use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone surveys of travellers. BMJ 313: 525528.[Crossref] [Google Scholar]
  9. Corbett EL, Doherty JF, Behrens RH, , 1996. Adverse events associated with mefloquine. BMJ 313: 1552.[Crossref] [Google Scholar]
  10. Steffen R, Fuchs E, Schildkneckht J, Naef U, Funk M, Schlgenhauf P, Phillips-Howard P, Nevill C, Stürchler D, , 1993. Mefloquine compared with other malaria chemoprophylactic regimens in tourists visiting east Africa. Lancet 341: 12991302.[Crossref] [Google Scholar]
  11. Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC, , 1993. Long-term malaria prophylaxis with weekly mefloquine. Lancet 341: 848851.[Crossref] [Google Scholar]
  12. Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, Herold M, Krebs B, Veit O, Allwinn R, Steffen R, , 2003. Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double-blind 4 arm study. BMJ 3327: 10781084.[Crossref] [Google Scholar]
  13. Gimenez F, Pennie RA, Koren G, Crevoisier C, Wainer IW, Farinotti R, , 1994. Stereoselective pharmacokinetics of mefloquine in healthy caucasians after multiple doses. J Pharm Sci 83: 824827.[Crossref] [Google Scholar]
  14. Na Bangchang K, Molunto P, Banmairuroi V, Thanavibul A, Karbwang J, , 1995. Pharmacokinetics of mefloquine when given as a single and two divided-dose regimens. Int J Clin Pharmacol Res XV: 215220. [Google Scholar]
  15. Simpson PM, , 1994. The construct validity of the cognitive drug research computerised assessment system. J Psychopharmacol 8 (Suppl): A20. [Google Scholar]
  16. Parrott AC, Hindmarsh I, , 1978. The LSEQ in psychopharmacological investigations. Psychopharmacology (Berl) 71: 173179.[Crossref] [Google Scholar]
  17. Boudreau EF, Flecenstein L, Pang LW, Childs GE, Schroeder AC, Ratnaratorn B, Phintuyothin P, , 1990. Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers. Clin Pharmacol Ther 48: 399409.[Crossref] [Google Scholar]
  18. Schlagenhauf P, Lobel H, Steffen R, Johnson R, Popp K, Tschopp A, Letz R, Crevoisier C, , 1997. Tolerance of mefloquine by Swissair trainee pilots. Am J Trop Med Hyg 56: 235240. [Google Scholar]
  19. World Health Organization, 2010. Guidelines for the Treatment of Malaria. Second Edition. Available at: http://www.who.int/malaria/publications/atoz/9789241547925/en/index.html. Accessed April 2, 2010. [Google Scholar]
  20. Rueangweerayut R, Pyae Phyo A, Uthaisin C, Socheat D, Quang Binh T, Tinto H, Penali L, Valecha N, Abdulla S, Thi Tien N, Borghini-Fuhrer I, Shin CS, , 2009. Efficacy and safety of pyronaridine/artesunate fixed-dose combination compared with mefloquine plus artesunate in patients with acute uncomplicated Plasmodium falciparum malaria: results of a pivotal Phase III trial. Trop Med Int Health 14 (Suppl 2): 45. [Google Scholar]
  21. Slutsker LM, Khoromana CO, Payne D, Allen CR, Wirima JJ, Heymann DL, Patchen L, Steketee RW, , 1990. Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome. Bull World Health Organ 68: 5359. [Google Scholar]
  22. Briand V, Bottero J, Noël H, Masse V, Cordel H, Guerra J, Kossou H, Fayomi B, Ayemonna P, Fievet N, Massougbodji A, Cot M, , 2009. Intermittent treatment for the prevention of malaria during pregnancy in Benin: a randomized, open-label equivalence trial comparing sulfadoxine-pyrimethamine with mefloquine. J Infect Dis 200: 9911001.[Crossref] [Google Scholar]
  23. Ferre S, Fuxe K, von Euler G, Johansson B, Fredholm BB, , 1992. Adenosine-dopamine interactions in the brain. Neuroscience 51: 501512.[Crossref] [Google Scholar]
  24. Ongini E, Fredholm BB, , 1996. Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci 17: 364372.[Crossref] [Google Scholar]
  25. Ferre S, Fedholm BB, Morelli M, Popoli P, Fuxe K, , 1997. Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 20: 482487.[Crossref] [Google Scholar]
  26. Morelli M, Carta AR, Jenner P, , 2009. Adenosine A2A receptors and Parkinson's disease. Handb Exp Pharmacoli 193: 589615.[Crossref] [Google Scholar]
  27. Hauser RA, Hubble JP, Truong DD, ; Istradefylline US-001 Study Group, 2003. Randomized trial the adenosine A(2A) receptor antagonist istradefyline in advanced PD. Neurology 12: 297303.[Crossref] [Google Scholar]
  28. Shiozaki S, Ichikawa S, Nakamura J, Kitamura S, Yamada K, Kuwana Y, , 1999. Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology (Berl) 147: 9095.[Crossref] [Google Scholar]
  29. Alva G, Cummings JL, , 2008. Relative tolerability of Alzheimer's disease treatments. Psychiatry (Edgmont) 5: 2736. [Google Scholar]

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  • Received : 21 Apr 2010
  • Accepted : 23 Aug 2010
  • Published online : 06 Dec 2010

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