History of C₂ monitoring in heart and liver transplant patients treated with cyclosporine microemulsion

Abstract 

Therapeutic drug monitoring of CsA has evolved since the introduction of CsA microemulsion. The purpose of the present review is to summarize the history of CsA concentration 2 hours postdose (C₂) monitoring in heart and liver transplantation. C₂ has been shown to be the best single time point that correlates with the area-under-the-curve, with a correlation coefficient (r²) ranging between .83 and .93. C₂ monitoring (300 to 600 ng/mL) has resulted in a significant clinical benefit in long-term heart and liver transplant patients compared to trough level (C₀) monitoring. Moreover, a C₂ range of 300 to 600 ng/mL resulted in a similar calcineurin inhibition compared to a C₂ range of 700 to 1000 ng/mL or a C₀ range of 100 to 200 ng/mL while being less injurious to renal function. In de novo liver transplant patients not receiving induction therapy, the achievement of a target C₂ of 850 to 1400 ng/mL by postoperative day 3 has resulted in a low acute rejection rate. Furthermore, C₂ monitoring has been associated with a lower rejection rate in hepatitis C virus (HCV)-negative patients and with an overall lesser severity of acute rejection compared to C₀ monitoring. In de novo heart transplant patients who receive antithymocyte globulin induction, a lower C₂ range may be sufficient to prevent rejection and renal dysfunction. Future studies should help to fine-tune the optimal C₂ range in heart or liver transplant patients receiving induction therapy and different maintenance immunosuppressive combinations.