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\begin{document}

\title{Population pharmacokinetic characteristics of tacrolimus in Chinese Han
lung transplant recipients and optimisation of dosing regimen}



\author[1]{Shouning Zhou}%
\author[1]{Qiaoyan Lian}%
\author[1]{Hui Xie}%
\author[2]{Yan-ping  Guan}%
\author[1]{Jianxing He}%
\author[1]{Li Wei}%
\author[1]{Chunrong Ju}%
\affil[1]{First Affiliated Hospital of Guangzhou Medical University}%
\affil[2]{Sun Yat-Sen University}%


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  \date{May 24, 2024}


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\begin{abstract}
Aim: To establish a population pharmacokinetic model and optimise
tacrolimus dosing regimens in Chinese Han lung transplant recipients.
Methods: Tacrolimus trough concentrations and clinical data of 70 adult
lung transplant recipients were collected. Population pharmacokinetic
analysis was performed using a nonlinear mixed effects model. A Monte
Carlo simulation was conducted to determine the optimal dosing regimen.
Results: The pharmacokinetics of tacrolimus could be best described by a
one-compartment model, with the CYP3A5 genotype, haematocrit (HCT), and
alanine transaminase (ALT) as significant covariates. The clearance of
tacrolimus in the CYP3A5 rapid and intermediate metabolisers were 3.03
and 1.99 times higher than those of CYP3A5 poor metaboliser,
respectively. When HCT decreased from 0.30 to 0.20, the clearance of
tacrolimus increased by 31.14\%, and the apparent volume of distribution
increased by 28.58\%. The clearance of tacrolimus decreased by 8.67\%
when ALT increased from 20 IU\selectlanguage{ngerman}·L-1 to 40 IU·L-1. Monte Carlo simulation
indicated that recipients with CYP3A5*1/*1 receiving 3.5 mg twice daily,
recipients with HCT \textless{} 0.2 receiving 5 mg twice daily, and
recipients with ALT \textless{} 4IU·L-1 received 3 mg twice daily, could
achieve the target concentrations of 10--15 ng·mL-1. Conclusions: A
population pharmacokinetic model of tacrolimus in Chinese Han lung
transplant recipients was successfully constructed. Recipients with the
CYP3A5*1/*1 genotype, low HCT value, and low ALT value after surgery
needed a higher maintenance dose to reach the therapeutic window, which
provided a reference for the formulation of individualised tacrolimus
regimen.%
\end{abstract}\selectlanguage{ngerman}%



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