A randomized comparison of chloroquine and chloroquine plus ketotifen in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.
The increasing resistance of Plasmodium falciparum to chloroquine (CQ) has created urgent needs for the evaluation of alternative antimalarial drugs that are effective, safe, readily available and affordable. Ketotifen, a histamine H(1)-receptor antagonist that reverses CQ resistance in P. falciparum in vitro, may potentially enhance the effects of CQ in vivo. The effects of oral treatment with CQ alone (30 mg/kg base given over 3 days) were compared with those of this CQ regimen combined with ketotifen fumarate (0.25 mg at presentation followed by 0.125 mg/kg every 8 h for 5 days). The subjects were 145 children aged 1-10 years who were suffering from acute, symptomatic, uncomplicated, P. falciparum malaria: 74 given CQ alone and 71 given CQ plus ketotifen (CQK). Although the mean fever-clearance time was significantly shorter following treatment with CQK than after treatment with CQ alone, all other therapeutic responses were similar in the two treatment groups. Among siblings in whom there was clustering of infections, the likelihood of cure was also similar in the two treatment groups. Retreatment of 17 CQ-treatment failures with CQK produced a cure in six children, and retreatment of 22 CQK-treatment failures with CQK produced a cure in eight children. Retreatment of all drug failures with a combination of amodiaquine plus pyrimethamine-sulfadoxine resulted in complete clearance of parasitaemia and symptoms within 2-3 days and a cure 'rate' of 100% on day 28. The prevalences and intensities of gametocytaemias on day 3 or days 3, 7 and/or 14 combined were similar in the two groups. Adverse drug reactions were always tolerable, and limited to pruritus, gastro-intestinal disturbances, drowsiness and weight gain; the latter two adverse effects were significantly more frequent in those treated with CQK than in those given CQ alone. Haematological and biochemical parameters were not adversely affected by either treatment regimen. The findings indicate that - at least at the dosing regimen used in the present study and among children with acute, uncomplicated, P. falciparum malaria from Ibadan - the addition of ketotifen to CQ produced little or no significant enhancement of the antimalarial effect of CQ.
Sowunmi
A
A
Department of Pharmacology and Therapeutics and Postgraduate Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria. malaria.iba@alpha.linkserve.com
D000208:Acute Disease; D000284:Administration, Oral; D000655:Amodiaquine / Q000008:administration & dosage; D000704:Analysis of Variance; D000962:Antimalarials / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D007665:Ketotifen / Q000008:administration & dosage* / Q000009:adverse effects; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy*; D008297:Male; D011739:Pyrimethamine / Q000008:administration & dosage; D012008:Recurrence; D013413:Sulfadoxine / Q000008:administration & dosage; D016896:Treatment Outcome
D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D007665:Ketotifen; D011739:Pyrimethamine