根据CYP3A5*1基因多态性指导肝移植术后他克莫司个体化用药的前瞻性对照研究

Individualized medication of tacrolimus after liver transplantation guided by CYP3A5*1 gene polymorphisms: a prospective controlled study

    摘要
  • 摘要:
      目的  评价基于细胞色素P450（CYP）3A5*1基因多态性指导肝移植术后他克莫司（FK506）个体化用药的安全性和有效性。
      方法  分析连续入组的100例首次行肝移植术受者的临床资料，并随机分为实验组和对照组，每组各50例。实验组术前对供、受者进行CYP3A5基因检测，并根据CYP3A5*1基因型确定FK506用药方案。观察术后7、14、28 d以及3、6、9、12个月两组受者FK506目标血药浓度达标率、肝功能恢复正常率以及随访过程中FK506调整用量次数。记录两组受者1年移植物存活率，及急性排斥反应、感染、急性肾损伤、消化道症状、新发高血压、新发糖尿病、感冒、皮疹等并发症的发生率。
      结果  两组受者术后7、14 d FK506目标血药浓度达标率比较，差异均有统计学意义（均为P < 0.05）。两组术后28 d及3、6、9、12个月FK506目标血药浓度达标率及术后7个观察时间点肝功能恢复正常率比较，差异均无统计学意义（均为P > 0.05）。两组受者随访期间FK506剂量调整次数比较，差异有统计学意义（P=0.021）。两组受者术后及随访期间1年移植物存活率和并发症发生率比较，差异均无统计学意义（均为P > 0.05）。
      结论  根据CYP3A5*1基因多态性指导肝移植术后FK506个体化用药是安全的，能在术后早期提高受者FK506目标血药浓度达标率，并且可以有效减少随访期间药量调整次数。

     

    Abstract:
      Objective  To evaluate the safety and efficacy based on cytochrome P450(CYP)3A5*1 gene polymorphisms in guiding the individualized medication of tacrolimus (FK506) after liver transplantation.
      Methods  Clinical data of 100 consecutively enrolled recipients who underwent liver transplantation for the first time were analyzed and randomly divided into experimental group and control group, with 50 cases in each group. The donors and recipients in the experimental group received preoperative CYP3A5 gene detection, and determined the FK506 medication regimen according to the CYP3A5*1 genotype. The compliance rate of FK506 target blood concentration, the recovery rate of liver function in the two groups of recipients at 7, 14, 28 d and 3, 6, 9, 12 months postoperatively, as well as the number of FK506 dosage adjustment during the follow-up were observed. The 1-year graft survival rate and the incidence of complications were recorded in both groups of recipients, such as acute rejection, infection, acute kidney injury, gastrointestinal symptoms, de novo hypertension, de novo diabetes, colds and rash, etc.
      Results  The differences of the compliance rate of FK506 target blood concentration between the two groups of recipients at 7, 14 d after operation were statistically significant (both P < 0.05). There was no statistically significant difference between the two groups in the compliance rate of FK506 target blood concentration at 28 d and 3, 6, 9, 12 months and the recovery rate of liver function at the 7 observation time points after operation (all P > 0.05). The difference between the two groups of recipients in number of FK506 dose adjustment during follow-up was statistically significant (P=0.021). There were no statistically significant differences in 1-year graft survival rate and incidence of complications between the two groups of recipients after operation and during follow-up (all P > 0.05).
      Conclusions  It is safe to guide individualized medication of FK506 after liver transplantation according to CYP3A5*1 gene polymorphism. It can increase the compliance rate of FK506 target blood concentration of recipients in the early postoperative stage, and can effectively reduce the number of dose adjustment duringfollow-up.

     

    • HTML全文
    • 参考文献(25)
    • 相关文章
    • 施引文献
  • 资源附件(0)

/

返回文章
返回