COMPARISON OF WHOLE-BLOOD AND SERUM LEVELS OF MEFLOQUINE AND ITS CARBOXYLIC-ACID METABOLITE

Because of the widespread presence of chloroquine-resistant Plasmodium falciparum malaria, mefloquine is now the recommended drug of choice for long-term malaria prophylaxis in these areas. Although several stu dies have compared plasma and whole blood concentrations of either mef loquine or its carboxylic acid metabolite, we report the first compari son of serum and whole blood levels in 86 Dutch marines taking 250 mg of mefloquine weekly for 18 weeks while deployed in western Cambodia. All samples were taken during steady-state and at 42-48 hr after the m ost recent dose. The concentration of mefloquine in serum (mean = 979 ng/ml) was significantly greater than in whole blood (mean = 788 ng/ml ) (P < 0.00001, by paired t-test) with an overall mean ratio of 1.28. The concentration of the metabolite in serum (mean = 3,039 ng/ml) was also significantly greater than in whole blood (mean = 1,390 ng/ml) (P < 0.00001, by paired t-test) with an overall mean ratio of 2.25. Thes e findings are similar to previous reports of plasma-to-whole blood le vels. Furthermore, we report that the within-individual ratios of the metabolite concentration to the mefloquine concentration were also fou nd to be significantly different in serum (3.79; P < 0.00001, by paire d t-test) and in whole blood (2.02; P < 0.00001, by paired t-test). Ap propriate attention must be given to these differences when comparing serum and whole blood concentrations of either mefloquine or its metab olite to avoid misinterpretation of their respective levels. Also, the determination of the relative mefloquine ratios in various blood flui ds, as well as the documentation of the metabolite levels and their ra tios, is critical to the appropriate interpretation of both chemoproph ylaxis and chemotherapy, especially in the presence of resistant strai ns.