Multiple-dose kinetic study of mefloquine in healthy male volunteers

250 mg mefloquine was administered orally once a week for 21 consecutive weeks to 5 volunteers. Blood samples were collected just before administration of the next dose, and the unchanged drug and its metabolite, Ro 21-5104, were measured in the plasma. The mean plasma levels minima in individual subjects measured at steady state were for mefloquine between 0.56 and 1.25 micrograms/ml, and for the metabolite between 1.47 and 5.55 micrograms/ml. The corresponding metabolite to mefloquine ratios ranged between 2.3 and 8.6. The half-life of mefloquine determined at the end of the trial agreed fairly well with values measured in single dose kinetics. This suggests that induction or inhibition of the metabolizing enzymes did not occur during the period of administration.