The impact of cyclosporine on the development of immunosuppressive therapy: perspective from a transplant nephrologist involved with the development of C2.

The availability of Neoral in place of Sandimmun offered better pharmacokinetics and improved results but emphasized the poor accuracy of trough levels as a tool for monitoring drug exposure and dosage adjustment. Subsequent studies confirmed that Neoral exposure correlated with clinical events and it was found that C2 was the single point that correlated best with exposure as determined by AUC(0-4h). Single and multicenter studies have now shown that C2 monitoring is practically feasible and that its use resulted in very low rates of acute rejection with excellent renal function. One retrospective comparison suggested that rates of acute rejection were lower with C2 than with C0 monitoring. This tool has now been shown to be effective in managing African-American renal transplants and those with delayed graft function. A very recent international randomized trial has shown equivalent rates of acute rejection in liver transplant recipients treated with both Neoral and Prograf. Studies now in progress will permit further refinement of target levels with the potential to improve long-term results.