Plasmodium falciparum kinetics during treatment with antimalarial drugs inchildren

Objective: To examine the kinetics of the disposition of Plasmodium falcipa rum during treatment with antimalarial drugs in 565 children presenting wit h acute, symptomatic, uncomplicated malaria. Methods: We conducted a prospective study using conventional principles for the disposition of drugs to characterise the kinetics of the disposition o f parasitaemia in children treated with antimalarial drugs. We also evaluat ed the relationship between the indices of parasite kinetics and the conven tional indices of therapeutic response to antimalarial drugs. Parasite kine tic parameters were estimated from parasite densities (parasite concentrati ons) by the noncompartmental method. Results: In drug-sensitive P. falciparum infections, the areas under the pa rasite density versus time curve (AUC(pd)) increased in proportion to paras ite load from 2500 to 320 000 asexual forms/mu l blood [p = 0.0004, analysi s of variance (ANOVA)], but there was no significant difference in the half -lives of reduction of parasitaemia (t1/2(pd)), the volume Of blood complet ely cleared of parasites per unit time (CLBpd) or the parasite density : AU C(pd)ratio, indicating that the kinetics of the disposition of parasitaemia were linear in the concentration range examined. In drug-sensitive infecti ons, AUC(pd), t1/2(pd) and CLBpd were similar for chloroquine, pyrimethamin e-sulfadoxine, halofantrine, chloroquine plus chlorphenamine (chlorpheniram ine), and cotrimoxazole (trimethoprimsulfamethoxazole). However, t1/2(pd) w as significantly lower (p = 0.00001, ANOVA) and CLBpd significantly higher (p = 0.00001, ANOVA) fur artemether when compared with other antimalarials used in sensitive infections, suggesting a relatively superior rapidity of action. In age, gender and parasite-density matched children, CLBpd was sig nificantly higher (p = 0.00003) in sensitive than in moderately or severely resistant infections. In treatment-sensitive infections, there was a corre lation between t1/2(pd) and parasite clearance time (PCT) [r(2) = 0.988, p = 0.00001]. The PCT: t1/2(pd) ratio was similar for all drugs (range 18-21; p = 0.072, ANOVA) and remained constant (p = 0.925, ANOVA) irrespective of PCT. A new index to classify the rapidity of action of antimalarial drugs in vivo based on the relationship between t1/2(pd) and PCT is presented. Conclusions: The kinetics of the disposition of P. falciparum ron parasitae mia in children with drug-sensitive infections are linear. The kinetic and other derived indices presented here may be used to evaluate and monitor th e therapeutic responses of infections and the rapidity of antimalarial acti on in children.