title: Atorvastatin does not affect the pharmacokinetics of cyclosporine in renal transplant recipients.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the possible influence of atorvastatin on the pharmacokinetics of cyclosporine (INN ciclosporin) and its main metabolites, AM1 and AM9, in renal transplant recipients.
  
  
  METHODS
  Whole blood samples from 18 renal transplanted patients on cyclosporine-based immunosuppressive therapy were collected prior to and after 4 weeks of treatment with atorvastatin (10 mg/day) and analysed with regard to both cyclosporine and its main metabolites, AM1 and AM9, using a specific chromatographic method with ultraviolet detection.
  
  
  RESULTS
  On average, AUC(0-12) [area under the whole blood concentration versus time curve in the dosing interval (0-12 h)] of cyclosporine was 5% (-16, 5) (90% confidence interval) lower upon co-administration with atorvastatin. No statistically significant changes in any of the calculated pharmacokinetic variables [AUC(0-12), maximum whole blood concentration (C(max)), whole blood concentration 12 h post dose (C(12)), time to C(max) (t(max)), terminal half-life (t(1/2))] for cyclosporine or the two metabolites, AM1 and AM9, upon atorvastatin treatment were observed. On average, atorvastatin did not affect the ratio between the CYP3A4-mediated metabolite AM9 and cyclosporine, suggesting that atorvastatin does not affect the CYP3A4 metabolism of cyclosporine to any significant extent. However, the influence of atorvastatin on the ratio between AM9 and cyclosporine showed large interindividual variability.
  
  
  CONCLUSIONS
  The results of this study indicate that atorvastatin does not, on average, affect cyclosporine pharmacokinetics in renal transplant recipients.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Oslo, PB 1068, Blindern, N-0316 Oslo, Norway. monicahe@farmasi.uio.no
authors.forename: Monica
authors.initials: M
authors.lastname: Hermann
authors.forename: Anders
authors.initials: A
authors.lastname: Asberg
authors.forename: Hege
authors.initials: H
authors.lastname: Christensen
authors.forename: Jan Leo Egge
authors.initials: JL
authors.lastname: Reubsaet
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D000069059:Atorvastatin; D016572:Cyclosporine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006207:Half-Life; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D016014:Linear Models; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D007166:Immunosuppressive Agents; D011758:Pyrroles; D016572:Cyclosporine; D000069059:Atorvastatin