*Purpose: Different initial dosing strategies were studied in Phase II/Phase III trials evaluating the pharmacokinetics, safety, and efficacy of LCPT in de novo kidney transplantation. The purpose of this analysis is to describe patterns in early tacrolimus trough concentrations at these doses versus those seen with twice daily immediate-release tacrolimus (IR-Tac).

*Methods: A post-hoc analysis of studies comparing LCPT to IR-Tac was conducted. LCPT was initiated at 0.14 (lower dose or “LCPT-LD”) or 0.17 mg/kg/day (higher dose, or LCPT-HD), while IR-Tac was initiated at 0.1 mg/kg/day, divided. Tacrolimus was initiated within 48 hours of transplant. Time to target range (defined as tacrolimus concentrations of 6 – 11 ng/mL), percent of patients within target range, and frequency of dose changes during the first weeks post-transplant are reported.

*Results: 569 de novo transplant recipients are included in the analysis (LCPT, n=298; IR-tac, n=271). Fewer patients received LCPT-LD due to the smaller, Phase II nature of the study. Tacrolimus dosing characteristics are shown in Table 1. Time to target level was lowest among patients initiated on LCPT-LD (5.06 days) and both LCPT groups exhibited significantly shorter time to obtain a tacrolimus concentration of at least 6 ng/mL compared to IR-Tac. More LCPT-LD patients remained within the target range during the first two weeks compared to the LCPT-HD patients, whereas more LCPT-HD patients reached trough concentrations above 11 ng/mL compared to LCPT-LD or IR-Tac immediately after transplant (Figure 1).

*Conclusions: LCPT-HD resulted in fewer patients with subtherapeutic tacrolimus concentrations early post-transplant but more patients with levels >11 ng/mL vs IR-Tac. LCPT-LD may represent a feasible initial dosing strategy that allows for rapid attainment of tacrolimus blood concentrations ≥6 ng/mL while exposing fewer patients to early trough concentrations >11 ng/mL versus LCPT-HD, though further evaluation in larger patient populations is needed to confirm this finding.

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