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A mathematical model to account for the blood-to-plasma distribution of cyclosporin A (CyA) in human blood was derived, and alterations in the blood-to-plasma distribution of CyA under several influencing conditions were examined using this model. The model was derived on the assumption that there are two CyA binding sites in human blood, which exist in plasma and cellular fractions. In the plasma fraction, the CyA binding sites are mainly lipoproteins (LPs), in which CyA exhibits nonsaturable, low affinity binding with LPs independent of drug concentration. In the cellular fraction, the binding site of CyA is the CyA binding protein (CBP), in which CyA shows a specific binding in a temperature dependent, saturable process. The results obtained from simulative studies agreed with previous reports on the blood-to-plasma distribution of CyA, indicating the usefulness of this approach. And also, this model may be used to predetermine individual variations in the blood-to-plasma distribution of the drug in renal transplant patients.

A model to account for the blood-to-plasma distribution of cyclosporin A in human blood.