Binding of artemether and lumefantrine to plasma proteins and erythrocytes

Abstract

The serum/plasma protein binding and blood distribution of artemether and lumefantrine was studied in vitro. The techniques used were the erythrocyte partitioning and ultrafiltration methods with 14C-labelled compounds. Both artemether and lumefantrine were found to be highly bound to proteins in serum, 95–98% and >99%, respectively. Under physiological protein concentrations, the distribution in blood showed that 33% of artemether was bound to α 1-acid glycoprotein, 17% to albumin, 12% to high density lipoproteins (HDL), 9.3% to low density lipoproteins (LDL) and 12% to very low density lipoproteins (VLDL), with binding capacities ( nKa) of 3.2×10 5, 6.2×10 3, 2.1×10 5, 1.7×10 6 and 2.0×10 7 l mol −1, respectively. 77% of lumefantrine was bound to HDL, 7.3% to LDL and 6.6% to VLDL, with binding capacities of 2.7×10 7, 2.6×10 7 and 2.4×10 8 l mol −1, respectively. A negligible fraction of lumefantrine was bound to albumin and α 1-acid glycoprotein. The fraction in erythrocytes was around 10% for both artemether and lumefantrine.