Plasma protein binding of tacrolimus in humans

An ultracentrifugation method was used for the determination of the tacrolimus (FK 506) free fraction in plasma. Samples of 400 μL were centrifuged for 6 h at 160 000 × g, and concentrations of [³H]tacrolimus were measured in the original plasma and in the second layer of the supernatant. The binding of tacrolimus in normal plasma averaged 73% and was independent of the drug concentration. Albumin (3.5%) binding averaged 44.4–57.0%, and α₁‐acid glycoprotein (100 mg/L) binding averaged 39%. Hepatic transplant patients exhibited 72.0% ± 3.6% binding of tacrolimus. Plasma protein binding is probably not an important factor in the disposition of tacrolimus.