NDT Advance Access published online on October 23, 2007
Nephrology Dialysis Transplantation, 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
Correspondence and offprint requests to: Correspondence and offprint requests to: 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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