Stereoselective pharmacokinetics of mefloquine in healthy caucasians after multiple doses

Mefloquine (MQ) is a chiral antimalarial agent effective against chloroquine‐resistant Plasmodium falciparum. It is commercially available as a racemic mixture of the (+) and (−) enantiomers for oral administration. The pharmacokinetics of the (+) and (−) enantiomers of MQ were studied in eight healthy volunteers after administration of a first oral dose of 250 mg of racemic MQ and at steady state after 13 repeated doses of 250 mg given at 1‐week intervals. Plasma samples were collected, and concentrations of each enantiomer were determined using a previously described achiralchiral double column‐switching liquid chromatographic method. At each time point, higher plasma concentrations values were found for the (−) enantiomer (p < 0.001). At steady state, C_max values of (−)‐MQ were higher than those of (+)‐MQ (1.42 ± 0.19 versus 0.26 ± 0.05 mg/L; p < 0.001). Similarly, the plasma concentrations 7 days after the final dose were higher for (−)‐MQ (1.01± 0.26 versus 0.11 ± 0.04 mg/L; p < 0.001). AUC values at steady state were also higher for (−)‐MQ (197.3 ± 36.7 versus 30.1 ± 8.9 mg/L·h; p < 0.001). The terminal half‐life values (T_1/2β) were longer for (−)‐MQ (430.4 ± 225.2 versus 172.8 ± 56.5 h; p < 0.001). This study shows that the pharmacokinetics of MQ is highly stereoselective.