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Data comparing long‐term effectiveness and safety of once‐daily tacrolimus formulations in de novo liver transplantation are scarce. We compared the effectiveness, pharmacokinetic profile, and safety of LCPT (Envarsus) and PR‐Tac (Advagraf) for up to 12 months post‐transplant. Adult de novo liver transplant recipients who started IR‐Tac (Prograf) and were converted to LCPT or PR‐Tac 3–5 days post‐transplant were included. Data from 163 patients were analyzed, 87 treated with LCPT and 76 with PR‐Tac. The incidence of treatment failure was 30.5% in the LCPT group versus 23.0% in the PR‐Tac group (p =.291). Biopsy‐proven acute rejection (BPAR) was reported in 26.8% of patients in the LCPT group and 17.6% in the PR‐Tac group (p =.166). Graft loss was experienced in one patient (1.2%) in the LCPT group and three patients (4.1%) in the PR‐Tac group (p =.346). Death was registered in three patients (3.7%) in the LCPT group and three patients (4.1%) in the PR‐Tac group (p >.999). Patients in the LCPT group showed 45.7% higher relative bioavailability (Cmin/total daily dose [TDD]; p <.01) with similar Cmin and 33.3% lower TDD versus PR‐Tac (p <.01). The evolution of renal function, safety profile, and the incidence of post‐transplant renal failure, dyslipidemia, obesity, hypertension, and diabetes mellitus were similar in patients treated with LCPT and PR‐Tac. In de novo liver transplant patients, LCPT and PR‐Tac showed comparable effectiveness with higher relative bioavailability, similar Cmin and lower TDD in the LCPT group. Renal function, safety, and post‐transplant complications were comparable in LCPT and PR‐Tac groups. [ABSTRACT FROM AUTHOR]

In this six-month randomized multicenter trial, we characterized cyclosporine pharmacokinetics and blood pressure profiles in maintenance liver transplant patients converting from twice-daily to once-daily cyclosporine dosing. A total of 60 patients were randomized as follows: group A (n = 14) maintained twice-daily dosing; group B (n = 24) converted to once-daily dosing at the same total daily dose as pre-conversion; and group C (n = 22) was treated the same as group B but with a 25% reduction in dose and C2 at two to three wk post-conversion. After conversion to once-daily dosing in groups B and C, trough blood levels (C0) did not change; whereas, C2 nearly doubled. The total daily area under the concentration–time curve AUC(0–24) increased by 29%. After the dose reduction in group C, the AUC(0–24) was similar to the pre-conversion value. Hence, a 25–30% dose reduction can be considered after conversion to once-daily dosing. In the study observation period in weeks 4–15, the median (25–75 percentile) C2 was 568 (469–750) ng/mL for group A; 1055 (840–1224) ng/mL for group B; and 764 (575–959) ng/mL for group C. Conversion to once-daily dosing was associated with a decrease in nighttime mean arterial blood pressure. [ABSTRACT FROM AUTHOR]