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 achiral-chiral 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, Cmax 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 x h; p < 0.001). The terminal half-life values (T1/2beta) 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.