Binding of artemether and lumefantrine to plasma proteins and erythrocytes

• Published in: European journal of pharmaceutical sciences Vol. 9; no. 1; pp. 9 - 16
• Main Authors: Colussi, Danielle, Parisot, Carole, Legay, François, Lefèvre, Gilbert
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.10.1999; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - metabolism; Antiparasitic agents; Artemether; Artemisinins; Benflumetol; Biological and medical sciences; Blood Proteins - metabolism; CGP 56697; Distribution; Dogs; Erythrocyte partitioning method; Erythrocytes - metabolism; Ethanolamines - metabolism; Fluorenes - metabolism; Humans; Lumefantrine; Medical sciences; Mice; Pharmacology. Drug treatments; Protein Binding; Rabbits; Rats; Sesquiterpenes - metabolism; Ultrafiltration; CGP 56697; Erythrocyte partitioning method; Ultrafiltration; Benflumetol; Distribution; Artemether; Lumefantrine; Protein binding; Antimalarial; Partition method; Albumin; Red blood cell; Lipoprotein; Serum protein; In vitro; Blood; Blood cell; Biological fixation; Parasiticid; α1-acid-Glycoprotein
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(99)00037-8

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.