Comparative efficacy and safety of two regimens of chlorpheniramine plus chloroquine in acute uncomplicated falciparum malaria in children

Objectives: To compare the therapeutic efficacy and tolerability of two reg imens of chlorpheniramine in combination with chloroquine in children with acute, symptomatic, uncomplicated falciparum malaria. A further aim was to examine the kinetics of the disposition of Plasmodium falciparum during tre atment with these regimens. Chlorpheniramine reverses chloroquine resistanc e in Plasmodium falciparum in vitro and in vivo. Methods: 96 children with acute, symptomatic, uncomplicated falciparum mala ria who were resident in an endemic area where the rate of chloroquine resi stance is 35 to 45% were treated in this randomised study. They received hi gh-dose chlorpheniramine (6mg + 12 mg/day in children aged less than or equ al to5 years; 8mg + 18 mg/day in those aged >5 years) plus chloroquine 10 m g/kg daily for 3 days (n = 47), or very high-dose (150% of high dose) chlor pheniramine plus chloroquine (n = 49) orally. Clinical and parasitological assessment was done daily on days 0-7 and day 14. Parasite disposition kine tics were evaluated from parasite concentrations using a noncompartmental m ethod. Results: Both high- and very high-dose chlorpheniramine plus chloroquine re gimens produced similar parasite (67.2 +/- 14.4 vs 67.2 +/- 14.4 h) and fev er (36.0 +/- 19.2 vs 36.0 +/- 19.2 h) clearance times and cure rates (95.7 vs 95.9%), respectively. The areas under the parasite density versus time c urve, the half-lives of parasitaemia and the volume of blood completely cle ared of parasites per unit time were also similar for the two treatment reg imens. Both treatment regimens were relatively well tolerated, but sleepine ss was significantly more frequent in the very high-dose group. Biochemical and haematological parameters were not adversely affected by either regime n. Conclusions: Very high-dose chlorpheniramine in combination with chloroquin e has no therapeutic advantage over high-dose chlorpheniramine in combinati on with chloroquine in this endemic area at the present time. The indices o f therapeutic responses derived from the evaluation of parasite kinetic par ameters produced conclusions similar to those of the conventional indices f or the measurement of therapeutic responses to antimalarial drugs.