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

IF 2.8 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Therapeutic Drug Monitoring Pub Date : 2025-06-01 Epub Date: 2024-11-15 DOI:10.1097/FTD.0000000000001272

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

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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 CYP3A5*3, ABCB1 3435, ABCB1 1236, and POR*28; 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.

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基因多态性在肾移植患者泊沙康唑与他克莫司药物相互作用中起重要作用。

背景：泊沙康唑（POSA）是第二代三唑类抗真菌药物，具有抑制CYP3A和p -糖蛋白的作用。本研究研究了POSA和他克莫司（TAC）在早期肾移植患者中的相互作用。方法：对22例肾移植受者进行POSA抗真菌治疗。统计分析以下指标：引入POSA前后TAC血药浓度(C)、剂量(D)、浓度-剂量比（C/D）；启动POSA后C/D的变化（ΔC/D）；CYP3A5*3、ABCB1 3435、ABCB1 1236、POR*28基因型；其他常规临床指标。结果：POSA启动后，TAC的C、D和C/D值分别为初始值的1.29倍、0.57倍和2.74倍。血浆POSA水平与ΔC/D呈线性相关。CYP3A5*3基因多态性对TAC的C、D和C/D有显著影响；但是，它不影响ΔC/D。ABCB1 3435基因多态性对ΔC/D有显著影响，ABCB1 3435 CC基因型患者的ΔC/D明显低于CT/TT患者。结论：在肾移植患者中，POSA和TAC之间的药物相互作用存在相当大的个体差异。CYP3A5*3和ABCB1 3435基因型及POSA血浆水平对POSA与TAC的相互作用有较大影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutic Drug Monitoring 医学-毒理学

CiteScore

5.00

自引率

8.00%

发文量

213

审稿时长

4-8 weeks

期刊介绍： Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.