title: Cyclosporine pharmacokinetics and dose monitoring after lung transplantation: comparison between cystic fibrosis and other conditions.
abstract: BACKGROUND
  In cystic fibrosis (CF), absorption of cyclosporine A (CsA) through the gastrointestinal tract is often impaired because of fat malabsorption. The aim of this study was to compare the steady-state pharmacokinetics of CsA and the inter- and intrasubject variability of CsA exposure in stable lung transplant recipients with and without CF and to determine the best single-time predictors of the area under the curve (AUC).
  
  
  METHODS
  Ten lung transplant recipients without CF and 10 lung transplant recipients with CF were studied. All patients received Neoral twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h postdose on three separate days within a 5-day period.
  
  
  RESULTS
  CsA exposure and pharmacokinetic variables were similar in the two groups, although exposure-per-milligram-per-dose was approximately 25% lower in CF patients. Coefficients of intersubject variability were numerically higher in CF patients, but the difference between groups did not reach significance. On the other hand, the maximum concentration (Cmax), the concentration 2 hours after administration (C2), AUC0-12, and AUC0-4 showed a twofold greater intrasubject variability in CF patients. CsA trough concentration did not predict accurately the AUC, but C2 was a good predictor of the AUC0-4 in both CF (r2=0.90) and non-CF (r2=0.78) patients.
  
  
  CONCLUSIONS
  Compared to patients without CF, patients with CF show a lower bioavailability of CsA and a greater intrasubject variability of Cmax, C2, and AUC. C2 is the best single-point predictor of the AUC0-4 in lung transplant recipients with and without CF.
authors.affiliation: Department of Chest Medicine, Erasme University Hospital, Brussels, Belgium.
authors.forename: Christiane
authors.initials: C
authors.lastname: Knoop
authors.forename: Ingrid
authors.initials: I
authors.lastname: Vervier
authors.forename: Philippe
authors.initials: P
authors.lastname: Thiry
authors.forename: Marc
authors.initials: M
authors.lastname: De Backer
authors.forename: John M
authors.initials: JM
authors.lastname: Kovarik
authors.forename: Annick
authors.initials: A
authors.lastname: Rousseau
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.forename: Marc
authors.initials: M
authors.lastname: Estenne
mesh_terms: D000328:Adult; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine