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In‐vitro Interaction of Artemisinin with Intact Human Erythrocytes, Erythrocyte Ghosts, Haemoglobin and Carbonic Anhydrase

The kinetics of the interaction of the antimalarial compound artemisinin with human erythrocytes, erythrocyte ghosts, haemoglobin and carbonic anhydrase were evaluated in‐vitro. Artemisinin plasma concentrations, measured by HPLC (high pressure liquid chromatography), decreased with time during incubations with whole blood and erythrocyte suspensions of varying haematocrit. Artemisinin concentrations declined more rapidly during incubations under oxygen‐poor as compared to oxygen‐rich conditions. Artemisinin concentrations did not decrease during incubation with erythrocyte ghosts suspended in plasma suggesting that the drug does not bind avidly to red blood cell membranes. There was no decline in concentrations of artemisinin in the presence of carbonic anhydrase. The disappearance of the drug in solutions containing haemoglobin was very rapid and was even more so when the incubation was performed under an argon‐ instead of oxygen‐rich atmosphere. The results suggest that drug blood clearance may be considered for inclusion in a pharmacokinetic model, but does not invalidate in‐vivo plasma concentration‐time data and their relevance for clinical effects. Furthermore, caution is advised when relating measurements of in‐vitro potency to drug levels in patients. Finally, the enhanced artemisinin disappearance when oxygen tension is low may contribute towards the explanation of the selective toxicity of the endoperoxide drugs to Plasmodium falciparum parasite.