Distribution and Protein Binding of FK506, a Potent Immunosuppressive Macrolide Lactone, in Human Blood and Its Uptake by Erythrocytes

Abstract

The distribution of FK506 in the blood was estimated in-vitro. At a drug level of 5 ng mL-1, FK506 mainly distributed in erythrocytes (95-98%) in dog, monkey and human blood, and its distribution was affected by drug concentration, temperature, and haematocrit values. In erythrocytes most of FK506 was distributed in cytoplasmic components and was bound strongly to a protein having a molecular weight of 10-11 kDa. The molecular weight of this protein agrees with FK506-binding protein found in various cells. Greater than 98.8% of FK506 was bound to the plasma proteins in all species studied. FK506 bound to various plasma proteins such as lipoproteins, globulins, alpha 1-acid glycoprotein and albumin.