title: Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, PO Box 1068 Blindern, 0316 Oslo, Norway. pal.falck@farmasi.uio.no
authors.forename: Pål
authors.initials: P
authors.lastname: Falck
authors.forename: Nils Tore
authors.initials: NT
authors.lastname: Vethe
authors.forename: Anders
authors.initials: A
authors.lastname: Asberg
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
authors.forename: Stein
authors.initials: S
authors.lastname: Bergan
authors.forename: Jan Leo Egge
authors.initials: JL
authors.lastname: Reubsaet
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
mesh_terms: D000328:Adult; D000368:Aged; D000069449:Cinacalcet; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D009281:Naphthalenes / Q000494:pharmacology*; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D009281:Naphthalenes; D016572:Cyclosporine; D009173:Mycophenolic Acid; D000069449:Cinacalcet; D016559:Tacrolimus