title: A Pilot Study of the Pharmacokinetics of the Modified-Release Once-Daily Tacrolimus Formulation Administered to Living-Donor Liver Transplant Recipients.
abstract: OBJECTIVE
  Sustained-release once-daily tacrolimus pharmacokinetics have not yet been characterized in de novo living-donor liver transplant recipients. Here, a 12-week, phase IV, single center, open-label, prospective pilot study was conducted to investigate the pharmacokinetics of this formulation in these patients.
  
  
  METHODS
  Patients received continuous intravenous infusion of tacrolimus on days 0 to 5 after transplant, which was followed by oral once-daily sustained-release tacrolimus. Two 24-hour pharmacokinetics profiles were generated for 10 patients on days 6 and 14. Secondary endpoints were minimum (trough level) and maximum whole blood concentrations, time to maximum concentration, and incidences of acute rejection, patient and graft survival, and adverse events.
  
  
  RESULTS
  Mean doses (± standard deviation) of sustained-release tacrolimus on days 6 and 14 were 0.14 ± 0.03 and 0.17 ± 0.04 mg/kg. Levels were within the recommended range throughout the study. When the actual dose was examined, area under the curve from 0 to 24 hours on day 14 was 1.8-fold higher than that on day 6 (423.9 vs 235.7 ng × h/mL). When tacrolimus was normalized to 0.1 mg/kg, area under the curve from 0 to 24 hours on day 14 was 1.5-fold higher than on day 6 (279.3 vs 183.4 ng × h/mL). When we used the actual dose, we found the correlation coefficient between area under the curve from 0 to 24 hours and trough level to be higher on day 6 (r = 0.87) than on day 14 (r = 0.691). No acute rejections, graft losses, patient deaths, or drug-related adverse events were reported.
  
  
  CONCLUSIONS
  Initial intravenous followed by sustained-release tacrolimus was safe and efficacious in living-donor liver transplant recipients. The mean area under the curve from 0 to 24 hours on day 14 was higher than previously reported; this difference may reflect cautious dosing regimens.
authors.affiliation: From the 1Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Gi-Won
authors.initials: GW
authors.lastname: Song
authors.forename: Sung-Gyu
authors.initials: SG
authors.lastname: Lee
authors.forename: Shin
authors.initials: S
authors.lastname: Hwang
authors.forename: Ki-Hum
authors.initials: KH
authors.lastname: Kim
authors.forename: Wan-Joon
authors.initials: WJ
authors.lastname: Kim
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Sin
authors.forename: Young-In
authors.initials: YI
authors.lastname: Yoon
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Tak
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004339:Drug Compounding; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010865:Pilot Projects; D011446:Prospective Studies; D056910:Republic of Korea; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus