Steady state pharmacokinetics of mefloquine in long-term travellers

  • Pennie R
  • Koren G
  • Crevoisier C
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Abstract

Mefloquine is an antimalarial drug with a 3-week elimination half-life, which has led to concerns that toxic accumulation may occur during weekly administration for long-term malaria chemoprophylaxis. Despite the endorsement of weekly mefloquine by the World Health Organization and the United States Centers for Disease Control, mefloquine pharmacokinetics have been incompletely studied in subjects taking the drug once weekly for more than 4 weeks. Our objective was to study plasma mefloquine concentrations in travellers taking mefloquine 250 mg once weekly for 3 months. Multiple mefloquine concentrations were measured by high pressure liquid chromatography following the 1st, 2nd and 10th to 13th of 13 weekly doses of 250 mg mefloquine taken by 15 Canadian travellers (median age 23 years; 6 male, 14 white). Steady state was achieved in all subjects by or before the 10th dose. Mefloquine pharmacokinetic values were comparable to those previously reported by other investigators. In 7 subjects, 2 peaks of mefloquine and metabolite concentration followed ingestion, suggesting redistribution of mefloquine. Mefloquine concentration 14 d after the last dose was 74% of the level 7 d after the last dose. In conclusion, pharmacokinetic values determined by this study support mefloquine weekly dosing for long-term malaria chemoprophylaxis; toxic accumulation does not occur and weekly dosing is associated with significantly higher trough levels than 14 d dosing© 1994, Oxford University Press. © 1994, Oxford University Press.

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Authors

  • Ross A. Pennie

  • Gideon Koren

  • Charles Crevoisier

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