title: Tacrolimus in cardiac transplantation: efficacy and safety of a novel dosing protocol.
abstract: BACKGROUND
  Although used for more than 20 years, optimal dosing strategies of most immunosuppressants have never been determined. Tacrolimus, one of the newer agents used in solid-organ transplantation, is gaining increasing popularity because of its ability to reverse refractory rejection in cyclosporine-treated patients and its favorable side-effect profile. As with many other immunosuppressive agents, absorption and metabolism vary between individuals, which complicates dosing.
  
  
  METHODS
  We hypothesized that a 1-mg dose of tacrolimus may be used to gauge each patient's metabolism. A novel dosing scheme was evaluated to establish the safety and efficacy of this approach. Outcomes were incidence of renal insufficiency and treatment efficacy as assessed by the rejection grade on the first endomyocardial biopsy.
  
  
  RESULTS
  The risk of renal insufficiency was low, with only a 3% rise in creatinine at 7 days posttransplant. The risk of renal insufficiency was highest during the first 3 days of tacrolimus therapy, and the change in tacrolimus level during this time was identified as the single best predictor of renal insufficiency. From days 4 to 7, the rise in tacrolimus level had much less influence on renal function. Ninety-two percent of patients had a low- or intermediate-grade first cardiac biopsy.
  
  
  CONCLUSIONS
  It was shown that this conservative initial dosing approach, which guarantees renal safety, is not associated with an increased risk of allograft rejection. We conclude that administration of tacrolimus via a tailored protocol soon after transplantation ensures a safe and effective means of immunosuppression.
authors.affiliation: Zena and Michael A. Weiner Cardiovascular Institute, Mt. Sinai Medical Center, Box 1030, New York, NY 10029, USA. David.Baran@mountsinai.org
authors.forename: David A
authors.initials: DA
authors.lastname: Baran
authors.forename: Ira
authors.initials: I
authors.lastname: Galin
authors.forename: David
authors.initials: D
authors.lastname: Sandler
authors.forename: Leal
authors.initials: L
authors.lastname: Segura
authors.forename: Judy
authors.initials: J
authors.lastname: Cheng
authors.forename: Mary C
authors.initials: MC
authors.lastname: Courtney
authors.forename: Rhodora
authors.initials: R
authors.lastname: Correa
authors.forename: Ming
authors.initials: M
authors.lastname: Chan
authors.forename: John T
authors.initials: JT
authors.lastname: Fallon
authors.forename: David
authors.initials: D
authors.lastname: Spielvogel
authors.forename: Steven L
authors.initials: SL
authors.lastname: Lansman
authors.forename: Alan L
authors.initials: AL
authors.lastname: Gass
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001706:Biopsy; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007668:Kidney / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011237:Predictive Value of Tests; D051437:Renal Insufficiency / Q000139:chemically induced / Q000175:diagnosis; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus