Pre-transplant pharmacokinetic profiling and tacrolimus requirements post-transplant

Aim:  To determine the proportion of patients achieving tacrolimus whole-blood concentrations of ≥10 ng/mL within 3 days of kidney transplantation, after randomization either to standard dosing (control group) or post-transplantation dosing guided by a 2-hour (C2) level following a preoperative tacrolimus dose (T2 group). Methods:  The first postoperative tacrolimus dose was given either according to standard care (control group) or 0.15 mg/kg b.d. if the pre-transplant C2 level was ≤20 ng/mL, 0.1 mg/kg b.d. if the C2 level was 21–59 ng/mL or 0.05 mg/kg b.d. if the C2 level was ≥60 ng/mL (T2 group). Subsequent dosing in both groups was based upon tacrolimus trough level monitoring. Participants received concomitant mycophenolate mofetil and steroids. Results:  Ninety patients were recruited, of which 84 were included in the analysis (control group n = 43; T2 group n = 41). There was no difference in the proportion of subjects achieving tacrolimus trough levels ≥10 ng/mL (82.9% Control vs 93.0% T2; P = 0.19) or between 10 and 15 ng/mL (41.5% Control vs 41.9% T2; P = 0.97) at day 3 post transplant. The T2 group achieved tacrolimus trough levels of ≥10 ng/mL significantly faster than the control group (100% achievement in 14 days (Control) versus 4 days (T2); P = 0.01). Conclusion:  Performing a pre-transplant tacrolimus C2 does not significantly increase the high proportion of subjects achieving 10 ng/mL tacrolimus concentrations by day 3 using routine protocols. However, compared with standard care, performing a pre-transplant tacrolimus C2 does lead to patients achieving a whole-blood concentration of ≥10 ng/mL sooner.