Kinetics of a new antimalarial, mefloquine

The kinetics of mefloquine hydrochloride were studied in 20 healthy adult male subjects after single oral doses of 250, 500, 1,000, and 1,500 mg. Whole blood concentrations of the drug were measured periodically for 83 days after drug administration. The resulting concentration/time data were analyzed to determine the rates of absorption and elimination of the drug. There was considerable variation in all of the estimated kinetic parameters, but differences did not appear to be related to the administered dose. Absorption was slow after administration of a tablet of the drug (mean ka, 4.37/day). When the drug was given in an aqueous suspension it was more rapidly and more completely absorbed, as indicated by a mean ka of 15.34/day and an area under the blood concentration/time curve 35% greater than with the same dose in tablet form. The volume of distribution was quite large (mean value for V/f, 13.30 1/kg). The therapeutic efficacy and prolonged duration of prophylactic effect of a single dose of mefloquine was consistent with the finding of a mean whole blood half-life (t½) of 13.89 days. There was considerable variation in the t½ within each dose group, with a range of 6.48 to 22.65 days. Because of the wide individual variation in the kinetics of mefloquine, it is anticipated that occasional treatment failures may occur when the drug is used for single-dose therapy on a large scale.