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Background  The objectives of the study were to elucidate the gender-specific distribution of mefloquine in cellular and fluid blood compartments when given at therapeutic dosage, to assess its correlation with the occurrence of treatment-related adverse events, and to explore the necessity of adjusting treatment guidelines for females.    Methods  The distribution of mefloquine following the administration of standard therapeutic doses (1,250 mg mefloquine in split dose) to 22 healthy Caucasian volunteers was assessed in whole blood, serum, plasma, red blood cells (RBCs), white blood cells, and platelets using high performance liquid chromatography.    Results  Plasma mefloquine concentrations after 14 hours were considerably higher in female subjects than in males (2,778  vs  1,017 ng/ml at H14), concordant with a significantly higher frequency, duration, and severity of adverse reactions. However, mean drug concentrations of RBC appeared slightly higher in male volunteers (857  vs  719 ng/ml). At H48, a similar situation prevailed, and at H168 the mefloquine concentrations in plasma continued to be higher in females compared to males (1,353  vs  666 ng/ml), while the concentrations of RBC were similar in females (389  vs  375 ng/ml). Since the observations relate to healthy individuals, they do not take into account selective uptake of mefloquine by  Plasmodium -infected erythrocytes as in the case of therapeutic drug use.    Conclusion  Although plasma mefloquine concentrations in female healthy volunteers are considerably higher and the concentrations of the RBCs are initially lower compared to males, they do not seem to justify an adjustment of treatment guidelines for mefloquine in female Caucasian individuals.

Gender-specific distribution of mefloquine in the blood following the administration of therapeutic doses