Background
Early after renal transplantation it is often challenging to achieve and maintain tacrolimus concentrations within the target range. Computerized dose individualization utilizing 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 eight weeks post-transplant. 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 seventy-eight 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 (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.
The correlation between WB-TAC and PBMC-TAC is modest during the first-year posttransplantation. Normalization of PBMC-TAC to cells or protein may yield different results. PBMC-TAC is increased 1.5 hours after dose at 1 week after transplantation, but not after 6 weeks or 1 year, indicating altered distribution kinetics.
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