ABSTRACT
In order to avoid the frequent side effects with injections of quinine in african children, empirical intrarectal administration of quinine (Quinimax, Sanofi Winthrop) has already been used successfully in Madagascar and Niger. In an attempt to optimise its use, a pharmacokinetic study was carried out with 66 children, 2 to 15 years old, admitted in pediatric unit for acute uncomplicated Plasmodium falciparum malaria, but warranting parenteral therapy. Children received Quinimax intrarectally (20 mg/kg/12h), intravenously (12,5 mg/kg in a slow infusion over 4 hours/12h) or intramusculary (12,5 mg/kg/12h). Plasma quinine concentrations were determined by HPLC. In this study, temperature and parasite clearance were similar in the 3 groups. A second randomized study was performed with 3 different dosages of intrarectal Quinimax: 8 and 13 mg/kg/8h and 20 mg/kg/12h. Temperature fell stably to normal at 36 hours with all regimens. Total clearance of parasitaemia was only obtained at 48 h with 30 mg/kg/12h regimen. Pharmacokinetic stimulation allowed to propose that intrarectal administration of Quinimax 20 mg/kg/8h would be a safe and effective regimen. A third approach studied the efficacy and pharmacokinetics of a new rectal quinine formulation (12,8 mg/kg/8h quinine gluconate) compared to IM and IV (8 mg/kg/8h) : at 36h, body temperature of all children was returned to normal and remained so until day 7. Parasitaemia expressed as a percentage of initial values was not different in the 3 groups after 48 h. At day 7, all the patients were aparasitaemics. The good tolerability and efficacy of this new intrarectal quinine formulation might allow to propose this route as an alternative to intramuscular route for the treatment of childhood malaria in Africa.