Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients.

BACKGROUND: The calcimimetic drug cinacalcet offers a novel therapeutic option to treat post-transplant hypercalcemia and hyperparathyroidism; however, the interaction with calcineurin inhibitors and mycophenolate has not been evaluated. METHODS: In the present study the effects of cinacalcet on the pharmacokinetics of cyclosporine A (CsA), tacrolimus (Tac) and mycophenolate were investigated in 14 renal transplant recipients with stable renal function (mean creatinine 126.4 +/- 45.3 micromol/L). The patients were treated with either CsA (n = 8) or Tac (n = 6) in combination with mycophenolate/azathioprine and steroids. Twelve-hour pharmacokinetic investigations to measure CsA and its six main metabolites, Tac and mycophenolate concentrations were performed before and after 1-week treatment with 30 mg cinacalcet once daily. RESULTS: Cinacalcet treatment induced a significant 14.3 +/- 12.1% decrease in Tac AUC(0-12) (P = 0.039). Tac C(max), T(max) and T(1/2) also tended to decrease. The pharmacokinetics of CsA and mycophenolate were not significantly affected by concomitant treatment with cinacalcet. However, the secondary CsA metabolite, AM19, showed a significant increase of 9.0 +/- 9.5% during cinacalcet treatment (P = 0.040). Renal function decreased significantly from 78 +/- 11 to 72 +/- 12 mL/min (P = 0.019) and correlated with the increased levels of metabolite AM19 in the CsA group. Renal function was unchanged in the Tac group. CONCLUSION: Cinacalcet treatment showed a moderate effect on the Tac, but not CsA or mycophenolate, pharmacokinetics after 1-week concomitant treatment. This interaction appears to have minor clinical relevance. However, it is advisable to monitor renal function in CsA-treated patients due to the observed decrease in renal function.