title: Monitoring of cyclosporine 2-hour post-dose levels in heart transplantation: improvement in clinical outcomes.
abstract: BACKGROUND
  Cyclosporine 2-hour post-dose (C2) monitoring is predictive of outcomes in solid-organ transplants. The purpose of this study was to determine C2 levels at various time points after heart transplantation and determine whether trough (C0) or C2 better predicts clinical outcomes.
  
  
  METHODS
  This was a 2-phase prospective study with paired determinations of cyclosporine levels at C0 and C2 in 58 heart transplant patients (46 men; mean age, 56 years). Phase I (6-month follow-up): cyclosporine monitored according to C0 levels (C2 blinded). Phase II (6-month follow-up): cyclosporine monitored according to C2 levels (C0 blinded). Clinical outcomes assessed were severe infections, rejection score, and renal dysfunction.
  
  
  RESULTS
  No differences were observed in renal function between the phases. In Phase I, 8 infections (4 severe) and in Phase II, 6 infections (2 severe) were detected. During Phase I, the C0 levels did not correlate (p = .96) with the presence (195 +/- 121 ng/ml) or not (197 +/- 100 ng/ml) of rejection. During Phase II, C0 levels did not correlate (p = .88) with the presence (204 +/- 85 ng/ml) or not (209 +/- 138 ng/ml) of rejection. During Phase I, C2 levels did correlate (p = 0.022) with the presence (777 +/- 326 ng/ml) or not (1,015 +/- 422 ng/ml) of rejection. During Phase II, higher C2 levels showed a significant correlation (p = 0.03) with no rejection (967 +/- 470 ng/ml vs 765 +/- 297 ng/ml, no rejection vs rejection, respectively).
  
  
  CONCLUSIONS
  High C2 levels were associated with less episodes of acute cellular rejection in patients post-heart transplantation. Monitoring with C2 levels is feasible and safe in terms of preservation of renal function and infection rates.
authors.affiliation: Division of Cardiology and Heart Transplant, Toronto General Hospital, ON, Canada. Diego.Delgado@uhn.on.ca
authors.forename: Diego H
authors.initials: DH
authors.lastname: Delgado
authors.forename: Vivek
authors.initials: V
authors.lastname: Rao
authors.forename: Jayne
authors.initials: J
authors.lastname: Hamel
authors.forename: Santiago
authors.initials: S
authors.lastname: Miriuka
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cusimano
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007239:Infections / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine