The in vitro effects of sulfadoxine/pyrimethamine and artemether/lumefantrine on the viscoelasticity of erythrocyte membrane of healthy females

Abstract

Fansidar ® (sulfadoxine/pyrimethamine) and Coartem ® (artemether/lumefantrine) are drugs that destroy malarial parasites and also produce free radicals which cause hemolysis of malaria-parasitized erythrocytes. This study investigated the effect of these drugs on the viscoelasticity of erythrocytes of ten healthy female subjects using the BioProfiler. The concentration for each of the two drugs were determined based on the therapeutic dose as normal, half the therapeutic dose as low and double the therapeutic dose as high. For Fansidar ® , the concentrations were 0.15/0.01 mg/ml (low), 0.30/0.02 mg/ml (normal) and 0.60/0.04 mg/ml (high) based on the adult therapeutic dose of 1500/75 mg of sulfadoxine/pyrimethamine in the drug combination. For Coartem ® , the concentrations were 0.03/0.19 mg/ml (low), 0.06/0.38 mg/ml (normal) and 0.12/0.76 mg/ml (high) based on the adult therapeutic dose of 320/1920 mg of artermether/lumefantrine in the drug combination. There was a statistically significant (p < 0.05) decrease in viscosity, elasticity and relaxation time with Coartem ® at normal and high doses. Fansidar ® also showed significant (p < 0.05) reductions in these parameters only in the high dose. This suggests that Coartem ® generated significant free radicals at normal and high doses, with Fansidar ® only in the high dose, resulting in increased hemolysis and ultimately reduced viscoelasticity.

In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood

“…The results of the present study in relation to the effects of artemether/lumefantrine on blood viscosity and elasticity were consistent with an earlier study 12 . Free radicals generated due to artemether increase haemolysis, resulting in a decrease of the haematocrit 11 .…”

“…The mechanism of action of artemether/lumefantrine involves its haemolytic effects on erythrocytes 11 . This combination has also been shown to reduce blood viscosity, elasticity and erythrocyte aggregation in vitro 12 . We undertook this in vitro study to investigate the effects of vitamin C on artemether/lumefantrine induced changes in whole blood viscosity and elasticity in healthy human volunteers.…”

Ascorbic acid co-administration with artemisinin based combination therapies in falciparum malaria

“…Artemisinins have also been shown to alter the viscoelastic properties of red cells. Richards et al 10 tested viscoelasticity of RBCs of ten healthy female subjects using Coartem® in three different drug concentrations; low, normal (therapeutic dose) and high. There was a significant decrease in viscosity and elasticity at normal and high doses.…”

“…There was a significant decrease in viscosity and elasticity at normal and high doses. The authors postulated a significant generation of free radicals at normal and high doses, which led to haemolysis and ultimately reduced viscoelasticity 10 .…”