Multiple-dose pharmacokinetics of the antimalarial drug Fansimef (pyrimethamine + sulfadoxine + mefloquine) in healthy subjects

Abstract

Fansimef is a new antimalarial combination containing pyrimethamine, sulfadoxine and mefloquine in the weight proportions 1 + 20 + 10. It has been designed to fight plasmodia resistant to the presently used antimalarial drugs and to counter the development of new resistant forms of the parasites. In the present study tablets containing 25 mg pyrimethamine, 500 mg sulfadoxine and 250 mg mefloquine were used. Six Brazilian volunteers received a loading dose of 2 tablets followed by 20 maintenance doses of 1 tablet at a dosage interval of 7 days. The pharmacokinetic evaluation of each of the three components was based on the assumption of an open linear two-compartment model. After the last maintenance dose the following kinetic parameters were determined for pyrimethamine, sulfadoxine and mefloquine, respectively: elimination half-life = 123, 179 and 550 h; volume of distribution in the postdistributive phase = 2.5, 0.15 and 18.6 1 X kg-1, and total systemic clearance = 14.0, 0.64 and 24.0 ml X h-1 X kg-1. All these values agree fairly well with those measured in previous single-dose kinetic studies. At steady state, Cmin values of each of the three components generally showed small variations. No unexpected accumulation of any of the three components was observed, indicating that induction or inhibition of metabolic enzymes did not occur during the trial.