Binding of iralukast to serum proteins and erythrocytes: measurements using ultrafiltration and an erythrocyte partitioning method.
The binding of iralukast to plasma (or serum) proteins and to erythrocytes was studied in vitro, at +37 degrees C, using the erythrocyte partitioning method (EPM) and/or ultrafiltration (UF) with 14C-labelled iralukast. Iralukast was highly bound in human and animal serum (>99%). Similar bound fraction values were obtained with the two methods: in whole human plasma (or serum) 99.8% (EPM) and 99.9% (UF), in albumin solution 99.8% (EPM and UF), in high density lipoprotein solution 97.3% (EPM) and 98.3% (UF), and in low density lipoprotein solution 97.2% (EPM) and 98.8% (UF). Moreover, the erythrocyte partitioning method allowed the evaluation of other binding parameters. The binding capacity (l/micromol) of proteins equalled 35 for low density lipoproteins, 3.6 for high density lipoproteins, 1.0 for albumin, 0.78 for alpha-1-acid glycoprotein, and 0.03 for gamma globulins. In whole blood, iralukast was distributed between plasma and erythrocytes in the proportion (%) 90/10. At physiological protein concentrations, iralukast was primarily bound to albumin (79%).
Colussi
D
D
Novartis Pharma S.A. Drug Metabolism and Pharmacokinetics, 2-4 rue Lionel Terray, B.P. 308, 92506 Rueil-Malmaison Cedex, France.
Parisot
C
C
Lefèvre
G
G
D001578:Benzopyrans / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D020024:Leukotriene Antagonists / Q000378:metabolism*; D011485:Protein Binding; D014462:Ultrafiltration
D001578:Benzopyrans; D001798:Blood Proteins; D020024:Leukotriene Antagonists; C067425:iralukast