Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients

Background. Triple drug treatment consisting of mycophenolate mofetil (MMF) , in a standard dose of 2 g daily, combined with cyclosporine (CsA) and pre dnisone, has become the standard immunosuppressive regimen after kidney tra nsplantation in many centers. The need for therapeutic drug monitoring of m ycophenolic acid (MPA) has not yet been established. Several drug interacti ons with MMF are known. We investigated the influence of CsA withdrawal on MPA trough levels in renal transplant patients. Methods. Fifty-two patients were treated with 1 g of MMF twice daily, and p rednisone and CsA targeted between 125 and 175 ng/ml for 6 months after tra nsplantation. At 6 months after transplantation, 19 patients were randomize d for continuation of triple therapy (group A), 19 patients discontinued Cs A (group B), and 14 patients discontinued prednisone (group C), We compared 12-hr fasted MPA trough levels at 6 and 9 months after transplantation wit hin and between these groups, Results. MPA trough levels during treatment with CsA, MMF, and prednisone w ere significantly lower than those during treatment with MMF and prednisone only (group B); median levels were 1.87 mg/L (range: 0.56-5.27) vs. 3.16 m g/L (range: 0.32-7.78), respectively (P=0.002), NIPA trough levels in group s A and C did not change between 6 and 9 months after transplantation; grou p A median levels were 1.87 (range: 0.31-4.32) vs. 1.53 mg/L (range: 0.36-3 .70), and group C median levels were 1.62 (range: 0.69-10.34) vs. 1.79 mg/L (range: 0.54-6.00), respectively. At 9 months after transplantation, patie nts in whom CsA was discontinued had higher MPA trough levels as compared w ith patients who continued the use of triple therapy (P=0.001) or patients in whom steroids were withdrawn (P=0.014), Conclusion. A significant increase of MPA trough levels was found after dis continuation of CsA (6 months after transplantation), resulting in almost a doubling of MPA trough levels at 9 months after transplantation, This resu lted in increased MPA levels in patients without CsA as compared to MPA lev els in patients continuing triple therapy or discontinuing prednisone.