Single dose kinetics of mefloquine in man. Plasma levels of the unchanged drug and of one of its metabolites

D E SchwartzM Gentilini


Oral single dose kinetics of mefloquine was investigated in 16 male volunteers, 3 Caucasians and 13 African natives. Unchanged mefloquine (= M) and one of its metabolites (= MM) were measured in the plasma. The apparent half-life of absorption of M ranged from 0.36 to 2.0 h, its terminal half-life of elimination from 15 to 33 days. Assuming complete systemic availability, an apparent volume of distribution of 14-29 liters x kg-1 and a total clearance of 18-39 ml x min-1 were derived. MM given orally to mice or rats showed at equal dose the same tolerance as mefloquine. Following oral administration of M to man, plasma levels of MM surpassed those of M, resulting in a 2.4-5.1 larger AUC. However, because of its much smaller apparent volume of distribution, MM may be anticipated to represent only a small percentage of the dose and therefore to contribute only to a minor extent towards the unwanted side effects of the drug.


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