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

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

Author by Prof. Christiana Sowunmi

Journal/Publisher: Clinical Drug Investigation

Volume/Edition: 20

Language: English

Pages: 317 - 325

Abstract

Objectives: To compare the therapeutic efficacy and tolerability of two regimens 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 treatment with these regimens. Chlorpheniramine reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo.

Methods: 96 children with acute, symptomatic, uncomplicated falciparum malaria who were resident in an endemic area where the rate of chloroquine resistance is 35 to 45% were treated in this randomised study. They received high-dose chlorpheniramine (6mg + 12 mg/day in children aged ?5 years; 8mg + 18 mg/day in those aged >5 years) plus chloroquine 10 mg/kg daily for 3 days (n = 47), or very high-dose (150% of high dose) chlorpheniramine plus chloroquine (n = 49) orally. Clinical and parasitological assessment was done daily on days 0–7 and day 14. Parasite disposition kinetics were evaluated from parasite concentrations using a noncompartmental method.

Results: Both high-and very high-dose chlorpheniramine plus chloroquine regimens produced similar parasite (67.2 ± 14.4 vs 67.2 ± 14.4 h) and fever (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 curve, the half-lives of parasitaemia and the volume of blood completely cleared of parasites per unit time were also similar for the two treatment regimens. Both treatment regimens were relatively well tolerated, but sleepiness was significantly more frequent in the very high-dose group. Biochemical and haematological parameters were not adversely affected by either regimen.

Conclusions: Very high-dose chlorpheniramine in combination with chloroquine has no therapeutic advantage over high-dose chlorpheniramine in combination with chloroquine in this endemic area at the present time. The indices of therapeutic responses derived from the evaluation of parasite kinetic parameters produced conclusions similar to those of the conventional indices for the measurement of therapeutic responses to antimalarial drugs.


Other Co-Authors