# Population dynamics analysis of the interaction between tacrolimus and voriconazole in renal transplant recipients

## TL;DR

This study develops a model to understand how tacrolimus and voriconazole interact in kidney transplant patients, helping to optimize drug dosing.

## Contribution

A novel population pharmacokinetic model was developed to analyze the interaction between tacrolimus and voriconazole in renal transplant recipients.

## Key findings

- Voriconazole concentration negatively correlates with tacrolimus clearance rate.
- Platelet levels positively correlate with tacrolimus clearance.
- Red blood cell count negatively correlates with tacrolimus clearance.

## Abstract

The concurrent administration of tacrolimus and voriconazole in kidney transplant recipients can lead to drug interactions, potentially resulting in severe adverse reactions. This study aimed to establish a robust population pharmacokinetic model to explore the interaction between tacrolimus and voriconazole in greater depth.

Tacrolimus blood samples and laboratory data were prospectively collected from eligible patients enrolled between April 2023 and April 2024, following predefined inclusion and exclusion criteria. Using Phoenix (version 8.1), a pharmacokinetic prediction model was developed. Model performance was assessed using model fitting plots, bootstrap analysis, and visual predictive checks (VPC).

This study ultimately included 51 eligible patients, with a total of 281 blood samples collected. Analysis revealed a significant negative correlation between voriconazole concentration (Cvrc) and tacrolimus volume of clearance rate (CL), a significant positive correlation between platelets (PLT) and tacrolimus clearance (CL), and a significant negative correlation between blood cells (RBC) and tacrolimus clearance (CL).

This study successfully established a population pharmacokinetic model for renal transplant patients concurrently receiving tacrolimus and voriconazole. The model demonstrated good predictive performance and offers valuable insights to clinicians for optimizing tacrolimus dosing in this patient population.