[Circulating forms of cyclosporin A]

The major circulating blood fraction of cyclosporin is localized in red blood cells. It is 58% for blood levels of less than 1,000 ng/ml. Beyond this concentration, a fall of this percentage is noticed which is related to a saturation phenomenon which occurs in its binding on an intracytosol protein, cyclophilin. Other fractions are distributed in the following manner: 27.5% on lipoproteins, 5% on albumin, 4% on polymorphonuclears, 5% on lymphocytes and 0.5% in the free state. There are various binding sites in the lymphocyte: in the membrane, cytosol on cyclophilin, and on the nucleus. The manner of binding on various plasma proteins, blood cells and platelets results in manifold pharmacological, pharmacokinetical, and toxicological results which are discussed here.