Evaluation of factors influencing the ratio of the trough blood concentration to dose level of everolimus in Japanese kidney transplant recipients.

Background: No factors influencing the blood everolimus (EVL) concentrations has been identified until date. Our aim was to identify factors that can affect the ratio of the trough blood concentration to dose level (C ₀ /D ratio) of EVL in kidney transplant recipients.
Methods: We retrospectively analyzed 448 patients who had undergone kidney transplantation and were subsequently being managed as our hospital between 2011 and 2015. Multivariate analysis were performed in an attempt to identify factors affecting the EVL C ₀ /D ratio.
Results: The numbers of patients receiving calcineurin inhibitor (CNI)-free regimen and regimen containing cyclosporine (CsA) or tacrolimus (TAC) were 47, 137 and 264 respectively. The EVL C ₀ /D ratio did not differ significantly between the TAC(+) group and the CNI-free group, while it was significantly higher in the CsA(+) group than the TAC(+) group (p < 0.0001) and CNI-free group (p = 0.0003). In the multivariate analysis, age, gender, diabetes mellitus as a cause of the end-stage renal disease (ESRD), CsA, serum creatinine, and hemoglobin were selected as factors affecting the EVL C ₀ /D ratio (R ²  = 0.269, p < 0.0001). Using the stepwise method, although mycophenolate mofetil treatment was selected, did not differ significantly according to multiple linear regression analysis. Furthermore, concomitant use of CsA was identified as the most impactful factor, based on the standardized partial regression coefficients (β = 0.341).
Conclusions: We obtained an indication of patient characteristics that influences the EVL C ₀ /D ratio. But the accuracy of the regression equation obtained from multiple regression analysis was poor (R ²  = 0.269), and it was not accurate enough to predict the EVL C ₀ /D ratio and use it for therapeutic drug monitoring.
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