NDT Advance Access originally published online on October 23, 2007
Nephrology Dialysis Transplantation 2008 23(3):1048-1053; doi:10.1093/ndt/gfm632
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Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients
1 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway 2 Department of Medical Biochemistry, Rikshospitalet Medical Center, Oslo, Norway 3 Department of Internal Medicine, Rikshospitalet Medical Center, Oslo, Norway 4 Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, Norway
Pål Falck, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, PO Box 1068 Blindern, 0316 Oslo, Norway. Tel: +47-22857578; Fax: +47-22854402; E-mail: pal.falck{at}farmasi.uio.no
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Abstract |
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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 µmol/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 AUC0–12 (P = 0.039). Tac Cmax, Tmax and T1/2 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.
Keywords: cinacalcet; cyclosporine; interaction; renal function; renal transplantation; tacrolimus
Received for publication: 5. 6.07
Accepted in revised form: 20. 8.07
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