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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1439232
Individualized Dosing Parameters for Tacrolimus in the Presence of Voriconazole: A Real-world PopPK Study
Provisionally accepted- 1 Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
- 2 China Pharmaceutical University, Nanjing, Jiangsu Province, China
Significant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens.We conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis.Nineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39 h -1 , 2690 L, and 42.87 L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F.Our findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.
Keywords: Tacrolimus, population pharmacokinetics, Voriconazole, Renal transplantation, Monte Carlo simulations
Received: 27 May 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Yan, Zhao, Sun, Li, Liu, ZHANG, Xie, Fang, Sandaradura and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Miao Yan, Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
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