title: Pharmacokinetics in stable heart transplant recipients after conversion from twice-daily to once-daily tacrolimus formulations.
abstract: BACKGROUND
  A prolonged-release formulation of tacrolimus for once-daily administration (tacrolimus QD) has been developed. This phase II, open-label, multicenter, prospective single-arm study compared the pharmacokinetics (PK) of tacrolimus in stable heart transplant patients before and after conversion from twice-daily tacrolimus (tacrolimus BID) to tacrolimus QD.
  
  
  METHODS
  Heart transplant recipients (≥6 months after transplant), previously maintained on tacrolimus BID-based therapy, received tacrolimus BID from Days 1 to 7 and were converted on a 1:1 (mg/mg) basis to tacrolimus QD. Five 24-hour PK profiles were collected (Days 1, 7, 8, 14, 21). Safety parameters were also evaluated.
  
  
  RESULTS
  Of 85 patients, 45 (50.6%) completed all 5 evaluable PK profiles. Steady-state tacrolimus area under the curve, 0 to 24 hours (AUC(0-24)) and minimum concentration (C(min)) were comparable for both formulations, with treatment ratio means of 90.5% (90% confidence intervals [CI], 86.4%-94.6%) and 87.4% (95% CI, 82.9%-92.0%), respectively (acceptance interval, 80%-125%). There was good correlation between AUC(0-24) and C(min) for tacrolimus QD (r = 0.94) and BID (r = 0.91). The relationship between these 2 parameters was also similar.
  
  
  CONCLUSIONS
  This study provides evidence for successful conversion from tacrolimus BID to QD on a 1:1 (mg/mg) total daily dose basis. Approximately one-third of patients may require dose adjustments. Both formulations were well tolerated, with stable renal function during the study. Adverse events were reported by approximately one-tenth of patients receiving tacrolimus BID and a quarter of those who received QD.
authors.affiliation: Department of Nephrology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Alloway
authors.forename: Johan
authors.initials: J
authors.lastname: Vanhaecke
authors.forename: Nizar
authors.initials: N
authors.lastname: Yonan
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.forename: Haissam
authors.initials: H
authors.lastname: Haddad
authors.forename: Gregorio
authors.initials: G
authors.lastname: Rábago
authors.forename: Wayne
authors.initials: W
authors.lastname: Tymchak
authors.forename: Beatriz
authors.initials: B
authors.lastname: Diaz Molina
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.forename: Hans
authors.initials: H
authors.lastname: Eiskjaer
authors.forename: Carmen
authors.initials: C
authors.lastname: Karpf
authors.forename: Nasrullah
authors.initials: N
authors.lastname: Undre
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014180:Transplantation / Q000502:physiology*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus