INTRODUCTION: Once-daily extended-release formulation of tacrolimus (QD-TAC) is expected to provide equal effects to the twice-daily formulation of tacrolimus (BID-TAC) with better drug adherence. According to the attached document, double dose of TAC should be administered once a day; however, the exact pharmacokinetic and the effect has not been thoroughly examined. Then we conducted a retrospective study of impact of two different formulation of TAC on kidney transplantation.
METHODS: One hundred twenty one kidney recipients who had not been clinically diabetic preoperatively were enrolled. Among them, 61 were introduced with BID-TAC (Group I) in conjunction with mycophenolate mofetile (MMF), corticosteroid (CS) and basiliximab (BSX), in contrast the rest 60 were with QD-TAC (Group II) with MMF, CS and BSX. In high-risk patients (ABO incompatible and/or donor HLA specific antibody positive) also required rituximab in both group. The dose of QD-TAC was adjusted according to area-under-the-curve of TAC (AUC0-24), which were initially thought as twice of AUC0-12 of BID-TAC. However, initial 7 patients in Group II were dropped off due to the conversion to cyclosporine because of presumable adverse event compared to 1 in Group I. Then the target AUC0-24 of QD-TAC was reduced to 60% of initial setting. The short-term outcome and feasibility within 1y after transplant of the eligible 53 patients in Group II were compared to 60 in Group I.
RESULTS: The patients characteristics were comparable except for recipient age (43.0 vs. 50.8 ys, Group I and Group II, respectively). The graft functions (serum creatinine and urine protein) were comparable. Numbers of acute rejection were also same (11 vs.13). Biopsy proven calcineurin nephrotoxicity does not differ in two Groups at any points (1m, 6m, 12m). The opportunities of viral infections (CMV disease, EBV, VZV, BKV, others) were comparable. Interestingly, QB-TAC did not affect glucose intolerance diagnosed by oral glucose tolerance test (diabetic range or impaired glucose tolerance) 1y post transplant compared to preoperative state (40.9 to 68.0%, p=0.0235 in Group I, 67.6 to 42.8%, p=0.08, in Group II).
CONCLUSION: QD-TAC can be used as the reduced dose, not double dose of BID-TAC. Long-term benefit as seen in glucose tolerance is expected other than better drug adherence because of reduced exposure of calcineurin inhibitor.
To cite this abstract in AMA style:Harada H, Fukuzawa N, Hotta K, Seki T, Togashi M. Once-Daily Extended-Release Formulation of Tacrolimus Does Not Require Double Dose of Twice-Daily Formulation of Tacrolimus in Kidney Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/once-daily-extended-release-formulation-of-tacrolimus-does-not-require-double-dose-of-twice-daily-formulation-of-tacrolimus-in-kidney-transplantation/. Accessed December 3, 2023.
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