title: C2 therapeutic drug monitoring of cyclosporine is a safe and feasible method in de novo heart transplant patients.
abstract: BACKGROUND
  The narrow therapeutic window of cyclosporine (CsA) requires close therapeutic drug monitoring (TDM). While C2-TDM has been established after renal and liver transplantations, clinical experience is limited for patients after de novo heart transplantation (HTX).
  
  
  METHODS
  In a retrospective study, we investigated 40 patients undergoing HTX; 34 patients received induction therapy using antithymocyte globulin (ATG Mérieux). Immunosuppression was administered with CsA (Sandimmun-Optoral), with dosages adjusted according to C2 levels (800-1100 ng/mL during the first 6 months and reduced to 400-600 ng/mL from the beginning of the first year). At different times TI (months 1-3). TII (months 12-14) TIII (months 24-26), and TIV (months 34-36), we obtained measures of acute cellular rejections (ARs), cytomegalovirus (CMV) infections, creatinine, and safety laboratory parameters.
  
  
  RESULTS
  The cumulative survival was 95% after 1 year, and 88% after 3.8 years. Eight ARs were diagnosed at a mean of 7.6 months after HTX in 7 patients. Twenty-four CMV infections/reactivations were verified. In 10 cases, treatment was started because of clinical symptoms. The mean creatinine values significantly rose in the early postoperative phase (TI: 1.23+/-0.47 mg/dL, TII: 1.49+/-0.41 mg/dL; P<.0001). Thereafter the creatinine values declined; however, this was not statistically significant (TIII: 1.38+/-0.57 mg/dL, TIV: 1.15+/-0.30 mg/dL). All other safety parameters showed no significant changes.
  
  
  CONCLUSIONS
  C2 allows individualization of immunosuppression with reduced CsA toxicity, but without loss in safety among de novo patients after HTX. We obtained freedom from severe AR, a low number of CMV infections, and excellent patient survival.
authors: Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany. tpuehler@kielheart.uni-kiel.de
authors: T
authors: T
authors: Puehler
authors: L
authors: L
authors: Goepel
authors: M
authors: M
authors: v Tschirschnitz
authors: U
authors: U
authors: Struckmeyer
authors: M
authors: M
authors: Ernst
authors: S
authors: S
authors: Ladenburger
authors: C
authors: C
authors: Schmid
authors: J
authors: J
authors: Cremer
authors: S W
authors: SW
authors: Hirt
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood; D012189:Retrospective Studies; D012449:Safety; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D008074:Lipoproteins; D016572:Cyclosporine; D002784:Cholesterol; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase