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

BACKGROUND & OBJECTIVES: The antimalarial combination drug artemether/lumefantrine has been shown to be effective against malaria parasite through its haemolytic action. This drug is sometimes co-administered with vitamin C in patients with malaria. Vitamin C is associated with antioxidant properties which would be expected to protect against haemolytic effects of this antimalarial drug. This study was designed to investigate in vitro effects of co-incubation of artemether/lumefantrine with vitamin C on the viscosity and elasticity of blood. METHODS: Blood was collected from 12 healthy female volunteers with normal haemoglobin genotype (HbAA). A Bioprofiler was used to measure the viscosity and elasticity of untreated blood samples (control) and samples exposed to artemether/lumefantrine (0.06/0.36 mg/ml) alone and with low or high dose vitamin C (equivalent to adult doses of 100 or 500 mg). RESULTS: artemether/lumefantrine significantly (p<0.05) reduced viscosity of blood from 4.72 ± 0.38 to 3.78 ± 0.17 mPa.s. Addition of vitamin C (500 mg) further reduced blood viscosity to 2.67 ± 0.05 mPa.s. The elasticity of blood was significantly (p<0.05) reduced from 0.33 ± 0.04 mPa.s to 0.24 ± 0.03 mPa.s by the antimalarial drug, and further reduced to 0.13 ± 0.02 mPa.s in the presence of vitamin C (500 mg). INTERPRETATION & CONCLUSIONS: Co-incubation of blood with vitamin C and antimalarial combination drug potentiates the haemolytic effects of the latter on reducing blood viscosity and elasticity in vitro. This may possibly have implications in relation to haemolysis in patients receiving vitamin C supplementation with artemether/lumefantrine during malaria therapy.

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

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.