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A Model to Account for the Variation in Cyclosporin Binding to Plasma Lipids in Transplant Patients

The usefulness of therapeutic monitoring for cyclosporin in transplant patients is still open to question due to variability of the data. One source of variability, the binding within plasma, was examined in renal transplant patients undergoing cyclosporin therapy. The fraction unbound varied between 0.04 and 0.13. A model based on physiochemical principles, involving concurrent partition of the drug between water, cholesterol, and triglyceride, was used to account for the variation in binding. Simulations using this model indicate that plasma cholesterol is a major factor contributing to the variability in fraction unbound and that the effect of triglyceride is less by a factor of four.