Merhaba Misafir

A pilot study of the pharmacokinetics of the modified-release once-daily tacrolimus formulation administered to living-donor liver transplant recipients


Objectives: 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. Materials and 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 x 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 x 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.

Yayınlandığı Kaynak : Experimental and Clinical Transplantation
  • Yıl : 2016
  • DOI : 10.6002/ect.2015.0227
  • Cilt : 14
  • ISSN : 1304-0855
  • Sayı : 4
  • eISSN : 2146-8427
  • Sayfa Aralığı : 412-418
  • IO Kayıt No : 52956
  • Yayıncı : Başkent Üniversitesi