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 × 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.