Cui Yi-Fan, Pan Yan, Zhu Min-Fang, Jiao Zheng
Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
J Pers Med. 2023 Apr 11;13(4):656. doi: 10.3390/jpm13040656.
Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate the pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation.
We enrolled 14 adult lung transplant recipients who were treated with tacrolimus and then intensively collected blood samples within a 12-h dosing interval. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of pathophysiological characteristics and CYP3A53 and CYP3A41G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the time-concentration curve (AUC).
Geometric mean of apparent clearance (CL/F) was 18.13 ± 1.65 L/h in non-CYP3A5*3/3 carriers, five times higher than that in CYP3A53/*3 carriers ( < 0.001). Furthermore, the tacrolimus concentration 4 h after administration had the strongest correlation with AUC (R = 0.979).
The pharmacokinetics of tacrolimus varied largely between patients during the early stage post-transplantation, which could be partially explained by CYP3A5*3 genetic polymorphisms.
尽管他克莫司已广泛应用于肺移植患者，但关于他克莫司在中国肺移植患者中的药代动力学研究报道较少。因此，我们旨在调查该患者队列在肺移植术后早期的药代动力学及影响因素。
我们纳入了14例接受他克莫司治疗的成年肺移植受者，然后在12小时给药间隔内密集采集血样。采用非房室分析计算他克莫司的药代动力学参数，并评估病理生理特征以及CYP3A53和CYP3A41G基因型对他克莫司药代动力学的影响。通过线性回归分析，我们研究了不同采样点他克莫司浓度之间的相关性，并测量了时间-浓度曲线下面积（AUC）。
非CYP3A5*3/3携带者的表观清除率（CL/F）几何平均值为18.13±1.65 L/h，是CYP3A53/*3携带者的五倍（<0.001）。此外，给药后4小时的他克莫司浓度与AUC的相关性最强（R = 0.979）。
移植术后早期患者之间他克莫司的药代动力学差异很大，这可能部分由CYP3A5*3基因多态性解释。
