Binding of artemether and lumefantrine to plasma proteins and erythrocytes.
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 1499%, respectively. Under physiological protein concentrations, the distribution in blood showed that 33% of artemether was bound to alpha(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 x 10(5), 6.2 x 10(3), 2.1 x 10(5), 1.7 x 10(6) and 2.0 x 10(7) lmol(-1), respectively. 77% of lumefantrine was bound to HDL, 7.3% to LDL and 6.6% to VLDL, with binding capacities of 2.7 x 10(7), 2. 6 x 10(7) and 2.4 x 10(8) lmol(-1), respectively. A negligible fraction of lumefantrine was bound to albumin and alpha(1)-acid glycoprotein. The fraction in erythrocytes was around 10% for both artemether and lumefantrine.
Colussi
D
D
Novartis Pharma S.A., Drug Metabolism and Pharmacokinetics, 2-4 rue Lionel Terray, B.P. 308, 92506, Rueil-Malmaison, France.
Parisot
C
C
Legay
F
F
Lefèvre
G
G
D000818:Animals; D000962:Antimalarials / Q000378:metabolism*; D000077549:Artemether; D037621:Artemisinins; D001798:Blood Proteins / Q000378:metabolism*; D004285:Dogs; D004912:Erythrocytes / Q000378:metabolism*; D004983:Ethanolamines / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism*; D006801:Humans; D000078102:Lumefantrine; D051379:Mice; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D012717:Sesquiterpenes / Q000378:metabolism*; D014462:Ultrafiltration
D000962:Antimalarials; D037621:Artemisinins; D001798:Blood Proteins; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes; D000077549:Artemether; D000078102:Lumefantrine