Pharmacokinetic properties of a once-daily formulation of tacrolimus in patients with renal transplantation

Abstract

The present study was designed to determine the pharmacokinetic profiles of a once-daily formulation of tacrolimus (CAS 104987-11-3; TAC-once) in patients before and after introduction of renal transplantation. Pharmacokinetic parameters for tacrolimus were almost comparable among patients receiving TAConce before, 2 weeks after and 3 weeks after renal transplantation. Among various parameters, C(trough) correlated most closely with the area under the concentration-time curve during 24 h (AUCo-24) (R2 = 0.82, P < 0.001), while no consistent correlation was observed between AUCo_24 and concentrations at 2 h or 4 h, or the dose of TAC-once. The clinical outcomes such as the incidence of acute re-jection, renal tissue injury and cytomegalovirus infection were evaluated during the first 3 weeks and 3 months after transplantation, and the data were compared with the historical data obtained from patients who had received the conventional twice-daily formulation of tacrolimus (TAC-twice). There were no significant differences in the incidence of such clinical outcomes between the two groups. These findings suggest that C(trough) is useful for therapeutic monitoring of tacrolimus in patients receiving TAC-once. In addition, pharmacokinetics and clinical outcomes were comparable between TAC-once and TAC-twice formulations.

Once-Daily Extended-Release Versus Twice-Daily Standard-Release Tacrolimus in Kidney Transplant Recipients

“…Patient Survival: Of the three de novo studies (13,21,22) that compared the twice-daily to the extended-release tacrolimus formulations, only two provided sufficient information for the meta-analysis. We found no significant differences in the overall patient survival between the two treatment arms (two studies, n=218; RR [CI], 1.02 [0.94Y1.10]; P=0.62; I 2 =0%; Fig.…”

“…Tacrolimus Level (C 0 and AUC 0Y24 ): Three (20%) observational studies (13,21,22) reported lower trough tacrolimus levels in recipients taking the extended-release formulation compared with those who received the twice-daily dosing within the first month after transplantation, which ranged from 7 to 13.04 ng/mL in daily dosing group compared with 9.1Y14.5 ng/mL in standard twice-daily dosing group at 1 week after transplantation and 10.4Y13.65 versus 11.8Y13.2 ng/mL in respective groups at 1 month.…”

Clinical experience with once–daily tacrolimus in de novo kidney transplant recipients from living donors in Japan: 1–year follow up

“…This difference could be due to either incomplete absorption across the gut wall or to a higher degree of metabolism on the first pass through the liver due to a slower rate of absorption [14]. Imanishi et al [15] reported that blood trough concentration correlated with AUC 0–24 in both OD TAC and BD TAC. Therefore, we adjusted the dose of tacrolimus in our study according to the blood trough concentration.…”