Impact of cyclosporine on the development of immunosuppressive therapy.

With the advent of cyclosporine (CsA) 20 years ago, graft survival increased considerably to more than 80% at 2 years posttransplant. The early formulation of CsA, Sandimmun, is effective in preventing organ rejection, although its absorption profile means it is subject to a high degree of variability. The development of a microemulsion formulation, Neoral, provided a therapy with superior efficacy in kidney, liver, and heart transplantation with an improved pharmacokinetic profile. Calcineurin inhibitors (CNIs), including CsA, have a narrow therapeutic range, so frequent blood measurements to control drug levels are required. Recent research has demonstrated that the measurement of blood CsA concentration at 2 hours postdosing--C2 monitoring--has the potential to optimize efficacy and reduce the side effects associated with CNI use. In heart and de novo kidney transplantation, C2 monitoring may help to further reduce the incidence of acute rejection, while in maintenance renal transplant recipients, C2 monitoring can help to detect overexposure and thus allows safe dose reduction, which may improve blood pressure and renal function. C2 monitoring thus facilitates a better balance between effective Neoral immunosuppression and unwanted side effects. Today, CsA remains the cornerstone of immunosuppression, and ongoing studies aim to further optimize patient management strategies with Neoral. With other trials evaluating the impact of Neoral in combination with newer therapies such as Certican, myfortic, and FTY720, the use of CsA in transplant recipients looks set to continue.