Adverse Effect of Rifampin on Quinine Efficacy in

The effects of adding rifampin to quinine were assessed in adults with uncomplicated falciparum malaria. Patients were randomized to receive oral quinine either alone (n 30) or in combination with rifampin (n 29). Although parasite clearance times were shorter in the quinine-rifampin-treated patients (mean stan-dard deviation, 70 21 versus 82 18 h; P 0.023), recrudescence rates were five times higher (n 15 of 23; 65%) than those obtained with quinine alone (n 3 of 25; 12%), P < 0.001. Patients receiving rifampin had significantly greater conversion of quinine to 3-hydroxyquinine and consequently considerably lower concen-trations of quinine in their plasma after the second day of treatment (median area under the plasma drug concentration-time curve from day zero to day 7 11.7 versus 47.5 g/ml day, P < 0.001). Rifampin significantly increases the metabolic clearance of quinine and thereby reduces cure rates. Rifampin should not be combined with quinine for the treatment of malaria, and the doses of quinine should probably be increased in patients who are already receiving rifampin treatment. Multidrug-resistant Plasmodium falciparum is an important public health problem in many areas where malaria is endemic. The efficacy of the major antimalarial drugs has declined in recent years, and the choice of effective antimalarial drugs i