Intrapatient CV of Tac AUC0-24 improved after converting from Tac BID to Tac QD in stable renal transplant patients, especially in patients with the CYP3A5*1/3 genotype. Given the very strict protocol of this PK study, this improvement is most likely due to the different intrinsic PK properties of Tac QD and Tac BID.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC 0-24 of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC 0-24 and C min for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.

Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimus bid). A once-daily prolonged-release formulation (tacrolimus qd) has been developed. This 6-week, randomized, phase 2, multicenter, open-label, prospective trial in primary liver transplant recipients investigated and compared the pharmacokinetics (PK) of tacrolimus for qd and bid formulations. All patients received tacrolimus-based immunosuppression (tacrolimus qd, n ¼ 67; bid, n ¼ 62). PK data were available for 77 patients (tacrolimus qd, n ¼ 45; bid, n ¼ 32). Tacrolimus area under the curve (AUC) from 0 to 24 hours (AUC 0-24 ) at equivalent doses was approximately 50% lower for tacrolimus qd than for bid on day 1 (146 versus 264 ngÁh/mL, respectively), but by day 14 was comparable between treatments (324 and 287 ngÁh/mL, respectively) with higher tacrolimus qd doses. There was a strong correlation between AUC 0-24 and concentration at 24 hours for tacrolimus qd and bid (r ¼ 0.92 and r ¼ 0.76, respectively). Furthermore, the relationship between these 2 parameters (ie, the slope of the line) was also similar for the 2 formulations. Efficacy endpoints were comparable for both formulations at 6 weeks with Abbreviations: AE, adverse event; AUC 0-24 , area under the curve from 0 to 24 hours; AZA, azathioprine; bid, twice daily; BPAR, biopsy-proven acute rejection; C 24 , concentration at 24 hours; C max , maximum concentration; C min , minimum blood concentration; MMF, mycophenolate mofetil; NEC, not elsewhere classified; PK, pharmacokinetics; qd, once daily; SD, standard deviation; T max , time to maximum concentration. This study and statistical analyses, and the editorial and project management services of Acumed involved in the preparation of this manuscript, were supported by Astellas Pharma Europe, Ltd., Staines, UK. L. Fischer, B. Gridelli, A. Roy, A. Vitale, A. Valdivieso, E. Varo, D. Seehofer, B. Ericzon, and K. Boudjema have declared no conflicts of interest. P. Trunečka has acted as study investigator and advisory board member for Astellas and has received speaker's fees. S. Lynch has received honoraria for chairing and speaking at international meetings for Astellas and JanssenCilag,

DIAMOND: multicenter, 24‐week, randomized trial investigating the effect of different once‐daily, prolonged‐release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged‐release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged‐release tacrolimus (0.15–0.175mg/kg/day) plus basiliximab; Arm 3: prolonged‐release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). Primary endpoint: eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan–Meier estimates of composite efficacy failure‐free survival were 72.0%, 77.6%, 73.9% in Arms 1–3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged‐release tacrolimus (0.15–0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged‐release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher‐dose prolonged‐release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable.