College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea.
Curr Pharm Des. 2024;30(39):3108-3115. doi: 10.2174/0113816128324199240730093415.
Sirolimus, one of the immunosuppressive drugs administered to renal transplant recipients, is metabolized by cytochrome P450 (CYP) 3A5. Accordingly, polymorphism is a genetic factor affecting sirolimus pharmacokinetics (PK). Therefore, we conducted a systematic review and meta-analysis on the association between sirolimus PK and polymorphism.
We searched for studies published up to 13 June 2024 from PubMed, Embase, Cochrane Library, and Web of Science. We reviewed studies on the relationship between polymorphism and weightadjusted trough concentration/dose (C /D) ratio and dosage of sirolimus in renal transplant recipients, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We evaluated mean differences (MDs) and 95% confidence intervals (CIs).
A total of seven studies were included. The weight-adjusted C0 /D ratio of sirolimus was significantly higher in patients with the rather than CYP3A5*1/1 or CYP3A51/*3 genotype (MD 95.27 ng/mL per mg/kg; 95% CI: 58.06, 132.47; I2 = 74%; p < 0.00001). Also, the weight-adjusted dosage of sirolimus was significantly lower in patients with the rather than or genotype (MD -2.60 × 10 mg/kg; 95% CI: -4.52, -0.69; I2 = 44%; = 0.008).
Our meta-analysis showed a significant effect for the genotype on weight-adjusted C /D ratio and dosage of sirolimus in adult renal transplant recipients.
西罗莫司是一种用于肾移植受者的免疫抑制剂药物，其代谢由细胞色素 P450（CYP）3A5 完成。因此，多态性是影响西罗莫司药代动力学（PK）的遗传因素。因此，我们对西罗莫司 PK 与多态性之间的关系进行了系统评价和荟萃分析。
我们检索了截至 2024 年 6 月 13 日PubMed、Embase、Cochrane 图书馆和 Web of Science 上发表的研究。我们根据系统评价和荟萃分析报告的首选项目指南，审查了关于 多态性与肾移植受者西罗莫司体重校正谷浓度/剂量（C / D）比值和剂量之间关系的研究。我们评估了平均差异（MD）和 95%置信区间（CI）。
共纳入 7 项研究。与 CYP3A5*1/1 或 CYP3A51/*3 基因型相比，携带 基因型的患者西罗莫司的体重校正 C0 / D 比值显著升高（MD 95.27ng/mL 每 mg/kg；95%CI：58.06，132.47；I2=74%；p<0.00001）。此外，与 或 基因型相比，携带 基因型的患者西罗莫司的体重校正剂量显著降低（MD-2.60×10mg/kg；95%CI：-4.52，-0.69；I2=44%； = 0.008）。
我们的荟萃分析表明，成人肾移植受者中 基因型对西罗莫司的体重校正 C / D 比值和剂量有显著影响。
