Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Med Princ Pract 2008;17:197–201 DOI: 10.1159/000117792 Enhanced Efficacy of Amodiaquine and Chlorpheniramine Combination over Amodiaquine Alone in the Treatment of Acute Uncomplicated Plasmodium falciparum Malaria in Children C.O. Falade a, b S.O. Michael a, b A.M.J. Oduola c a Departments of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, and b Clinical Pharmacology Department, University College Hospital, Ibadan, Nigeria; c Special Program for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland combination of AMQCP could be a better alternative to AMQ alone as a companion drug in artemisinin-based combina- tion therapies. Copyright © 2008 S. Karger AG, Basel Introduction Chloroquine, a 4-aminoquinoline, has been widely used in sub-Saharan Africa in the treatment of malaria because of its easy availability, affordability and good safety profile [1, 2]. The rising prevalence of chloroquine- resistant parasites has, however, compromised its efficacy [1–3], which had led to the change from chloroquine as first-line treatment to the more effective artemisinin- based combination therapy (ACT) in Nigeria and many other African countries [3, 4]. However, some non-antimalarial drugs have been shown to reverse chloroquine resistance in Plasmodium falciparum in vitro and in animal models [5–8]. These include verapamil: a calcium channel antagonist; desip- ramine: a tricyclic antidepressant and chlorpheniramine (CP): a histamine type 1 receptor blocker. In vitro poten- tiation of the schizonticidal effect of some other amino- quinoline drugs, mondesethylamodiaquine, amopyro- quine and bisquinoline WR 268,668, by desipramine has also been reported [9, 10] . Mondesethylamodiaquine is the main active metabolite of amodiaquine (AMQ), while Key Words Amodiaquine, efficacy  Chlorpheniramine  Falciparum malaria Abstract Objective: To evaluate the comparative efficacy of amodia- quine (AMQ) alone and the combination of AMQ and chlor- pheniramine (CP) in the treatment of acute uncomplicated malaria in children. Subjects: Of the 110 children enrolled in the study, 103 with acute uncomplicated malaria, aged 6 months to 12 years, were evaluated using the 14-day modi- fication of the WHO field test. The patients were randomized to 2 groups. Group 1 received supervised treatment with AMQ alone (10 mg AMQ base/kg daily for 3 days), while group 2 received supervised treatment with AMQ (same dose as group 1) plus CP (AMQCP) for 7 days. Results: Both treatment regimens were well tolerated and no patient was withdrawn as a result of recurrent vomiting or drug-related adverse events. There was no significant difference in mean fever and parasite clearance times. The cure rates at day 7 were 90.2 versus 100% (  = 0.027) for AMQ versus AMQCP, while the day 14 cure rates were 85.9 versus 98.1% for AMQ versus AMQCP, respectively (  = 0.016). Conclusion: The combination of AMQ plus CP proved significantly more ef- fective than AMQ alone in the treatment of acute uncompli- cated falciparum malaria, most probably due to the en- hancement of the antimalarial effect of AMQ by CP. The Received: April 11, 2007 Revised: September 23, 2007 Dr. Catherine Olufunke Falade Clinical Pharmacology Department University College Hospital/University of Ibadan Ibadan (Nigeria) Tel. +234 80 3326 4593, E-Mail fallady@skannet.com © 2008 S. Karger AG, Basel 1011–7571/08/0173–0197$24.50/0 Accessible online at: www.karger.com/mpp