Improved Tacrolimus Target Concentration Achievement Using Computerized Dosing in Renal Transplant Recipients--A Prospective, Randomized Study

Abstract

Background: Early after renal transplantation, it is often challenging to achieve and maintain tacrolimus concentrations within the target range. Computerized dose individualization using population pharmacokinetic models may be helpful. The objective of this study was to prospectively evaluate the target concentration achievement of tacrolimus using computerized dosing compared with conventional dosing performed by experienced transplant physicians.

Methods: A single-center, prospective study was conducted. Renal transplant recipients were randomized to receive either computerized or conventional tacrolimus dosing during the first 8 weeks after transplantation. The median proportion of tacrolimus trough concentrations within the target range was compared between the groups. Standard risk (target, 3-7 μg/L) and high-risk (8-12 μg/L) recipients were analyzed separately.

Results: Eighty renal transplant recipients were randomized, and 78 were included in the analysis (computerized dosing (n = 39): 32 standard risk/7 high-risk, conventional dosing (n = 39): 35 standard risk/4 high-risk). A total of 1711 tacrolimus whole blood concentrations were evaluated. The proportion of concentrations per patient within the target range was significantly higher with computerized dosing than with conventional dosing, both in standard risk patients (medians, 90% [95% confidence interval {95% CI}, 84-95%] vs 78% [95% CI, 76-82%], respectively, P < 0.001) and in high-risk patients (medians, 77% [95% CI, 71-80%] vs 59% [95% CI, 40-74%], respectively, P = 0.04).

Conclusions: Computerized dose individualization improves target concentration achievement of tacrolimus after renal transplantation. The computer software is applicable as a clinical dosing tool to optimize tacrolimus exposure and may potentially improve long-term outcome.

Trial registration: ClinicalTrials.gov NCT02010320.

Figure 1

Observed tacrolimus trough concentrations in the Computer Group and Control Group over time after transplantation in A) standard risk patients and B) high-risk patients. Solid lines show the median concentration. Shaded areas represent the target range. Solid gray line represents the middle of the target range.

Figure 2

Mean percentages of tacrolimus concentrations within the target range per week after transplantation for the Computer Group and Control Group in A) standard risk patients (n=67) and B) high-risk patients (n=11). The numbers within the bars show the mean percentage within range. Vertical lines represent 95% confidence intervals.