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基因多态性在肾移植患者泊沙康唑与他克莫司的药物相互作用中起重要作用。

Gene Polymorphisms Play an Important Role in the Drug Interaction Between Posaconazole and Tacrolimus in Renal Transplant Patients.

作者信息

Hu Nan, Guan Mengmeng, Gu Bin, Yang Xuping, Qian Qing, Zhao Di, Xue Hui, Jiang Jingting

机构信息

Department of Pharmacy, The Third Affiliated Hospital of Soochow University, Changzhou.

College of Pharmaceutical Sciences, Soochow University, Suzhou.

出版信息

Ther Drug Monit. 2025 Jun 1;47(3):330-336. doi: 10.1097/FTD.0000000000001272. Epub 2024 Nov 15.

DOI:10.1097/FTD.0000000000001272
PMID:40341589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12061382/
Abstract

BACKGROUND

Posaconazole (POSA), a second-generation triazole antifungal drug, inhibits CYP3A and P-glycoprotein. Here, the interaction between POSA and tacrolimus (TAC) in patients undergoing early renal transplantation was studied.

METHODS

Twenty-two renal transplant recipients who received POSA as antifungal therapy were studied. The following indicators were analyzed statistically: the blood concentration (C), dose (D), and concentration-dose ratio (C/D) of TAC before and after introducing POSA; the change of C/D (ΔC/D) after starting POSA; the genotypes of CYP3A53, ABCB1 3435, ABCB1 1236, and POR28; other routine clinical indicators.

RESULTS

After starting POSA, the C, D, and C/D values of TAC were 1.29, 0.57, and 2.74 times the original values, respectively. A linear correlation was observed between the plasma levels of POSA and ΔC/D. The CYP3A5*3 gene polymorphism showed a significant impact on C, D, and C/D of TAC; however, it did not affect the ΔC/D. Polymorphism of the ABCB1 3435 gene had a significant effect on ΔC/D, and patients with the CC genotype in ABCB1 3435 had significantly lower ΔC/D than the CT/TT patients.

CONCLUSIONS

In renal transplant patients, considerable interindividual variability was observed in the drug interactions between POSA and TAC. The genotypes of CYP3A5*3 and ABCB1 3435 and the plasma level of POSA had strong impact on the interaction between POSA and TAC.

摘要

背景

泊沙康唑（POSA）是第二代三唑类抗真菌药物，可抑制细胞色素P450 3A（CYP3A）和P-糖蛋白。在此，对早期肾移植患者中泊沙康唑与他克莫司（TAC）之间的相互作用进行了研究。

方法

对22例接受泊沙康唑作为抗真菌治疗的肾移植受者进行了研究。对以下指标进行了统计分析：引入泊沙康唑前后他克莫司的血药浓度（C）、剂量（D）和浓度-剂量比（C/D）；开始使用泊沙康唑后C/D的变化（ΔC/D）；CYP3A53、ABCB1 3435、ABCB1 1236和POR28的基因型；其他常规临床指标。

结果

开始使用泊沙康唑后，他克莫司的C、D和C/D值分别为原来的1.29倍、0.57倍和2.74倍。观察到泊沙康唑的血浆水平与ΔC/D之间存在线性相关性。CYP3A5*3基因多态性对他克莫司的C、D和C/D有显著影响；然而，它不影响ΔC/D。ABCB1 3435基因多态性对ΔC/D有显著影响，ABCB1 3435基因CC基因型患者的ΔC/D显著低于CT/TT基因型患者。

结论

在肾移植患者中，泊沙康唑与他克莫司之间的药物相互作用存在相当大的个体差异。CYP3A5*3和ABCB1 3435的基因型以及泊沙康唑的血浆水平对泊沙康唑与他克莫司之间的相互作用有强烈影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/58f08508d5d0/tdm-47-330-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/d8b84bfb9c8a/tdm-47-330-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/173f46cbf472/tdm-47-330-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/023d72bf6542/tdm-47-330-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/58f08508d5d0/tdm-47-330-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/d8b84bfb9c8a/tdm-47-330-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/173f46cbf472/tdm-47-330-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/023d72bf6542/tdm-47-330-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/361d/12061382/58f08508d5d0/tdm-47-330-g004.jpg

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