Optimizing tacrolimus therapeutic drug monitoring in Tunisian kidney transplant recipients: exploring the variability in bioavailability and the correlation between pharmacokinetic parameters

Ghaith Aloui; Rym Charfi; Mouna Daldoul; Syrine Ben Hammamia; Mouna Ben Sassi; Mohamed Zouari; Hanene Eljeberi; Riadh Daghfous; Emna Gaies; Sameh Trabesli

doi:10.1515/dmpt-2024-0043

Article

Optimizing tacrolimus therapeutic drug monitoring in Tunisian kidney transplant recipients: exploring the variability in bioavailability and the correlation between pharmacokinetic parameters

Ghaith Aloui , Rym Charfi , Mouna Daldoul , Syrine Ben Hammamia , Mouna Ben Sassi , Mohamed Zouari , Hanene Eljeberi , Riadh Daghfous , Emna Gaies and Sameh Trabesli

Published/Copyright: December 16, 2024

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From the journal Drug Metabolism and Personalized Therapy Volume 39 Issue 4

Abstract

Objectives

While the existing literature extensively covers the topic of tacrolimus variability, it remains crucial to gather data that are tailored to the Tunisian population. Our primary goal was to assess the variability in tacrolimus bioavailability using the Cp(0)/weight dosage ratio in Tunisian kidney transplant patients. We also aimed to determine the correlations between blood trough level (Cp(0)) and the area under the concentration–time curve (AUC0–12 h) in this cohort.

Methods

This retrospective study included patients treated with oral tacrolimus for the prevention of organ rejection between 2009 and 2023. The correlation between parameters was analyzed through a Pearson coefficient and a regression model. We assessed the inter- and intraindividual variability by calculating the coefficient of variation for patients with at least three samples.

Results

Analysis of 2,124 samples revealed a weak correlation (R=0.121) between Cp(0) and weight dosage. We found that 79.3 % of patients exhibited high variability in the Cp(0)/weight dosage ratio. A strong correlation (R=0.797) was found between Cp(0) and the AUC0–12 h. We also found that 47.6 % of patients showed high variability in the AUC0–12 h/Cp(0) ratio.

Conclusions

This study underscores the necessity for individualized therapeutic drug monitoring in Tunisian kidney transplant recipients due to the high variability in the Cp(0)/weight dosage ratio. The AUC0–12 h/Cp(0) ratio is proposed as a more consistent parameter for therapeutic drug monitoring, offering potential improvements in tacrolimus therapy management.

Keywords: therapeutic drug monitoring; tacrolimus; kidney transplant; bioavailability; blood trough level; the area under the concentration–time curve

Corresponding author: Ghaith Aloui, Department of Clinical Pharmacology, National Centre Chalbi Belkahia of Pharmacovigilance, Tunis, Tunisia; and Department of Pharmacy of the Main Military Training Hospital of Tunis, Montfleury; 1008 Tunis, Tunisia, E-mail: ghaith.aloui@fphm.u-monastir.tn

Acknowledgments

We extend our heartfelt gratitude to all the personnel of the Department of Clinical Pharmacology at the National Centre Chalbi Belkahia of Pharmacovigilance, Tunis, Tunisia, not only for their invaluable contributions to this study but also for their unwavering dedication to the department’s day-to-day work.

Research ethics: Our research obtained approval from the Institutional Review Board at Charles Nicolle Hospital in Tunis, Tunisia.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: Large language models, including ChatGPT by OpenAI, were used to assist in refining the text and ensuring clarity in some sections of the manuscript. The generation and analysis of data were conducted independently of these tools.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

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Received: 2024-06-24

Accepted: 2024-10-18

Published Online: 2024-12-16

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2024-0043

Keywords for this article

therapeutic drug monitoring; tacrolimus; kidney transplant; bioavailability; blood trough level; the area under the concentration–time curve