# Clinical Factors Influencing Tacrolimus Metabolism and Blood Level Early After Kidney Transplantation—A Comparison of Three Different Tacrolimus Formulations

## TL;DR

This study compares how different forms of tacrolimus affect blood levels in kidney transplant patients, finding that factors like age and intestinal markers influence drug exposure.

## Contribution

The study identifies formulation-specific clinical and physiological factors influencing tacrolimus metabolism post-transplant.

## Key findings

- Age independently influences tacrolimus exposure in Prograf-treated patients.
- Advagraf-treated patients show associations between tacrolimus exposure and eGFR, induction therapy, LPS, and dose.
- Envarsus-treated patients show tacrolimus exposure linked to age and FABP-2 levels.

## Abstract

Background: Optimal tacrolimus dosing in the early post-transplant period is still challenging. We prospectively studied the possible associations between selected parameters of recipient body composition, markers of intestinal permeability and tacrolimus dosing and blood level in kidney transplant recipients (KTRs) treated with three different tacrolimus formulations. Methods: When discharged from hospital immediately after kidney transplantation, markers of intestinal permeability, body composition parameters and tacrolimus blood level were assessed in 165 KTRs treated with Prograf, Advagraf or Envarsus. Results: In the stepwise multivariate analysis performed in patients treated with Prograf, only age independently influenced the tacrolimus exposure expressed as area under the curve (AUC). In patients treated with Advagraf, eGFR (rpartial = 0.291; p < 0.05), antithymocyte globulin (vs. basiliximab) induction (rpartial = 0.445; p < 0.001), lipopolysaccharide (LPS) level (rpartial = 0.393; p < 0.01) and drug dose (rpartial = 0.433; p < 0.01) were independently associated with tacrolimus AUC. In patients treated with Envarsus, only age (rpartial = −0.365; p < 0.05) and fatty-acid-binding protein (FABP-2) level (rpartial = −0.364; p < 0.05) were independently associated with the tacrolimus AUC. Conclusions: We confirmed the significant association between markers of intestinal permeability and tacrolimus exposure in KTRs who underwent early post-transplant conversion from Prograf to Advagraf or Envarsus. This may suggest that the planned tacrolimus conversion from the twice-daily to the once-daily formulation should be performed later (at least 3 months after transplantation) to avoid unnecessary tacrolimus blood level instability.