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Antimicrobial Agents and Chemotherapy, May 2003, p. 1509-1513, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1509-1513.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Adverse Effect of Rifampin on Quinine Efficacy in Uncomplicated Falciparum Malaria

Department of Tropical Medicine, Faculty of Tropical Medicine,¹ Faculty of Pharmacy, Mahidol University, Bangkok, Thailand,² College of Pharmacy, Western University of Health Sciences, Pomona, California 91766,³ Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom⁴

Received 10 April 2002/ Returned for modification 3 November 2002/ Accepted 4 February 2003

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 ± standard 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 concentrations 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 µg/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.

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