# Analysis of Tacrolimus Clearance in Patients with Kidney Transplants from Romania

## TL;DR

This study identifies genetic and clinical factors affecting tacrolimus clearance in kidney transplant patients from Romania to improve personalized dosing.

## Contribution

A population pharmacokinetic model for tacrolimus in Romanian kidney transplant recipients, incorporating CYP3A4 genotype and hematocrit.

## Key findings

- CYP3A4*1/*1.001 genotype significantly impacts tacrolimus clearance.
- Hematocrit is a significant covariate for intercompartmental clearance.
- Incorporating these factors can improve dosing strategies and therapeutic monitoring.

## Abstract

Background/Objectives: Tacrolimus is a key immunosuppressant in kidney transplantation, but its high interindividual pharmacokinetic variability complicates dosing. This study aimed to develop a population pharmacokinetic model and identify the factors explaining variability to optimize tacrolimus therapy in Romanian kidney transplant recipients. Methods: The study included 106 kidney transplant recipients treated at Fundeni Clinical Institute (2022–2024). Tacrolimus blood levels were measured using immunoassays, while gene polymorphisms of CYP3A4, CYP3A5, and ABCB1 were identified by real-time polymerase chain reaction. Results: Patients with CYP3A4*1/*1.001 impact clearance (RSE = 11.8%), while hematocrit was a significant covariate for intercompartmental clearance (RSE = 6.14%). Conclusions: Incorporating CYP3A4*1/*1.001 genotype and hematocrit into dosing strategies can improve therapeutic drug monitoring and personalize immunosuppressive therapy.