title: Assessment of cyclosporine pharmacokinetic parameters to facilitate conversion from C0 to C2 monitoring in heart transplant recipients.
abstract: BACKGROUND
  Cyclosporine (CsA) 2-hour postdose (C2) monitoring is recommended to assess CsA exposure and predict clinical outcomes among heart transplant recipients. We correlated pharmacokinetic parameters and clinical outcomes in stable long-term heart transplant recipients monitored with C0 to develop an algorithm to convert patients from C0 to C2 monitoring.
  
  
  METHODS
  Paired CsA C0-C2 measurements and serum creatinine levels were obtained from 35 heart transplant recipients more than 2 years posttransplantation (mean 8.8+/-4.7 years).
  
  
  RESULTS
  The mean CsA dose and C0, C2, and C0/C2 ratio were 85+/-23 mg/12 hours, 123+/-41 ng/mL, 572+/-274 ng/mL and 4.8+/-2.1, respectively. C0 correlated weakly with C2 (r=.42, P=.011). The CsA dose correlated better with C2 (r=.58; P<.001) than with C0 (r=.37; P=.026). A good correlation was noted between C2 and the C2/C0 ratio (r=.73; P<.001), but none between C0 and the C2/C0 ratio. A borderline significant inverse correlation was noted between C0 and the worst endomyocardial biopsy score (r=-.34; P=.045), whereas none was noted with C2. Serum creatinine level did not correlate with either C2 or C0. Among patients with C0 within our target of 100 to 150 ug/L, six had C2 above 300 to 600 ug/L as suggested by the literature.
  
  
  CONCLUSIONS
  In long-term heart transplant recipients, we could not identify a single pharmacokinetic parameter that could be used to develop an algorithm to convert from C0 to C2 monitoring; however, C2 may be better than C0 for identifying patients at risk of overexposure to CsA.
authors: Department of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors: R A
authors: RA
authors: Davies
authors: J P
authors: JP
authors: Veinot
authors: K
authors: K
authors: Williams
authors: H
authors: H
authors: Haddad
authors: A
authors: A
authors: Baker
authors: J
authors: J
authors: Donaldson
authors: C
authors: C
authors: Pugliese
authors: C
authors: C
authors: Struthers
authors: R G
authors: RG
authors: Masters
authors: P J
authors: PJ
authors: Hendry
authors: T
authors: T
authors: Mesana
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D016572:Cyclosporine / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine