title: The value of C2 monitoring in stable renal allograft recipients on maintenance immunosuppression.
abstract: BACKGROUND
  Cyclosporin A (CyA) is a drug with a narrow therapeutic window and highly variable pharmacokinetics. Therapeutic drug monitoring is essential and conventionally has been guided by trough levels (C0). Recent evidence indicates that a single blood concentration measurement 2 h after CyA administration (C2) is a more accurate predictor of drug exposure and clinical events than determination of C0. To date, limited prospective data are available with respect to risks and benefits of C2 monitoring in renal transplant recipients, and little experience exists with C2 monitoring in maintenance patients.
  
  
  METHODS
  In 127 long-term renal allograft recipients, we determined C2 levels in addition to conventional C0 and observed clinical outcome over a period of 13.6 +/- 3.1 months. To determine the precision of monitoring, we repeatedly determined C0 and C2 levels in 46 stable patients without dose change.
  
  
  RESULTS
  Clinical outcome was excellent (patient survival 100%, graft survival 97%), with only two borderline rejections, although C2 levels (564 +/- 186 ng/ml) were lower than recommended so far for maintenance patients. We found no significant differences in C2 levels between patients with rejection and CyA toxicity. Receiver operating characteristic (ROC) analysis showed no prediction for risk of rejection, toxicity or infection by C2 levels. Repeated determinations of both C0 and C2 levels in 46 patients revealed a high intra-patient variability. In these patients, the coefficient of variation for C2 was only marginally better compared with C0.
  
  
  CONCLUSIONS
  We conclude that in maintenance patients, C2 concentrations between 500 and 600 ng/ml are well tolerated and provide effective and safe rejection prophylaxis. Although mean C2 levels do not seem to be helpful in identifying patients at risk for rejection, they may be useful to detect over-immunosuppression and to improve long-term allograft survival further by reducing CyA nephrotoxicity.
authors.affiliation: Department of Nephrology, Charité, Humboldt University, Schumannstrasse 20-21, D-10117 Berlin, Germany. gunilla.einecke@charite.de
authors.forename: Gunilla
authors.initials: G
authors.lastname: Einecke
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mai
authors.forename: Lutz
authors.initials: L
authors.lastname: Fritsche
authors.forename: Torsten
authors.initials: T
authors.lastname: Slowinski
authors.forename: Johannes
authors.initials: J
authors.lastname: Waiser
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D016572:Cyclosporine / Q000276:immunology / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine