Pre-transplant pharmacokinetic profiling and tacrolimus requirements post-transplant

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 (C(2) ) level following a preoperative tacrolimus dose (T2 group).

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 C(2) level was ≤20 ng/mL, 0.1 mg/kg b.d. if the C(2) level was 21-59 ng/mL or 0.05 mg/kg b.d. if the C(2) 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.

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).

Performing a pre-transplant tacrolimus C(2) 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 C(2) does lead to patients achieving a whole-blood concentration of ≥10 ng/mL sooner.