目的建立快速检测CYP3A5基因型的新方法及其临床应用。方法针对CYP3A5不同基因型特异性位点设计引物,采用等位基因特异性PCR方法(Allele specific PCR,AS-PCR)进行扩增,通过琼脂糖凝胶电泳分辨不同基因型,并检测临床标本100例,与一代测...目的建立快速检测CYP3A5基因型的新方法及其临床应用。方法针对CYP3A5不同基因型特异性位点设计引物,采用等位基因特异性PCR方法(Allele specific PCR,AS-PCR)进行扩增,通过琼脂糖凝胶电泳分辨不同基因型,并检测临床标本100例,与一代测序法比对两个方法的一致率。结果新方法检测100例临床标本中,CYP3A5基因型*1/*1型15例;*1/*3型26例;*3/*3型59例,结果与一代测序法一致,一致率100%。结论通过AS-PCR检测CYP3A5基因型,操作简便,结果易于判断,可应用于临床。展开更多
目的通过筛选真实世界中非瓣膜性房颤(NVAF)合并肾功能不全[15<肌酐清除率(CL_(cr))≤60 mL·min^(-1)]患者联用利伐沙班致出血风险增加的药代动力学相互作用(PK-DDI)药品,以促进临床合理用药。方法通过检索文献(PubMed、Web of ...目的通过筛选真实世界中非瓣膜性房颤(NVAF)合并肾功能不全[15<肌酐清除率(CL_(cr))≤60 mL·min^(-1)]患者联用利伐沙班致出血风险增加的药代动力学相互作用(PK-DDI)药品,以促进临床合理用药。方法通过检索文献(PubMed、Web of Science、中国知网、万方数据、维普网)、说明书、2021年欧洲心律协会指南、Lexicomp数据库总结利伐沙班PK-DDI目录;采用回顾性队列研究,收集2022年11月1日至2023年10月31日在首都医科大学宣武医院住院并服用利伐沙班的NVAF合并肾功能不全患者,根据是否使用利伐沙班PK-DDI药品分为PK-DDI组和非PK-DDI组。其中PK-DDI药品限定为P-gp和/或CYP3A4抑制剂,随访3个月,比较2组患者有效性和安全性结局。结果共计22类141种药品,根据是否需调整剂量分类,需要禁用、慎用药品65种和无需调整剂量药品76种。研究共纳入患者143例,PK-DDI组出血发生率高于非PK-DDI组(P<0.05),PK-DDI组与非PK-DDI组的缺血性卒中发生率差异无统计学意义(P>0.05)。PK-DDI组主要的出血性事件为临床相关非大出血(8例,61.5%),用药后30 d内出血发生率为38.7%,涉及药品包含胺碘酮、银杏叶提取物、氟康唑、伏立康唑、奥希替尼。结论利伐沙班PK-DDI涉及多种药品,主要靶点为P-gp和CYP3A4。肾功能不全患者服用利伐沙班时,联用P-gp和/或CYP3A4抑制剂增加出血风险。利伐沙班应避免与银杏叶提取物、伏立康唑联用。利伐沙班与胺碘酮、氟康唑、奥希替尼联用需严密监测,如凝血酶原时间、抗凝血(Xa)因子水平或利伐沙班血药浓度。展开更多
BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher T...BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.AIM To evaluate the predictive value of the TAC concentration-to-dose(C0/D)ratio for identifying CYP3A5 poly-morphisms in renal transplant recipients.METHODS Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103(Hanoi,Vietnam)were included in this retrospective study.Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.RESULTS The CYP3A53/3 genotype was identified in 37 patients(43%),CYP3A51/3 in 40 patients(46.5%),and CYP3A51/1 in 9 patients(10.5%).Patients carrying the CYP3A51/3 or CYP3A51/1 genotype,classified as fast metabolizers(CYP3A5 expressers),had significantly lower TAC C0 concentrations and C0/D ratios compared to slow meta-bolizers(CYP3A53/3 genotype)at multiple time points during follow-up(all P<0.001).Notably,the TAC C0/D ratio obtained on day 1(0.91)was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6%and a specificity of 84.6%.CONCLUSION This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms,which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.展开更多
文摘目的建立快速检测CYP3A5基因型的新方法及其临床应用。方法针对CYP3A5不同基因型特异性位点设计引物,采用等位基因特异性PCR方法(Allele specific PCR,AS-PCR)进行扩增,通过琼脂糖凝胶电泳分辨不同基因型,并检测临床标本100例,与一代测序法比对两个方法的一致率。结果新方法检测100例临床标本中,CYP3A5基因型*1/*1型15例;*1/*3型26例;*3/*3型59例,结果与一代测序法一致,一致率100%。结论通过AS-PCR检测CYP3A5基因型,操作简便,结果易于判断,可应用于临床。
文摘目的通过筛选真实世界中非瓣膜性房颤(NVAF)合并肾功能不全[15<肌酐清除率(CL_(cr))≤60 mL·min^(-1)]患者联用利伐沙班致出血风险增加的药代动力学相互作用(PK-DDI)药品,以促进临床合理用药。方法通过检索文献(PubMed、Web of Science、中国知网、万方数据、维普网)、说明书、2021年欧洲心律协会指南、Lexicomp数据库总结利伐沙班PK-DDI目录;采用回顾性队列研究,收集2022年11月1日至2023年10月31日在首都医科大学宣武医院住院并服用利伐沙班的NVAF合并肾功能不全患者,根据是否使用利伐沙班PK-DDI药品分为PK-DDI组和非PK-DDI组。其中PK-DDI药品限定为P-gp和/或CYP3A4抑制剂,随访3个月,比较2组患者有效性和安全性结局。结果共计22类141种药品,根据是否需调整剂量分类,需要禁用、慎用药品65种和无需调整剂量药品76种。研究共纳入患者143例,PK-DDI组出血发生率高于非PK-DDI组(P<0.05),PK-DDI组与非PK-DDI组的缺血性卒中发生率差异无统计学意义(P>0.05)。PK-DDI组主要的出血性事件为临床相关非大出血(8例,61.5%),用药后30 d内出血发生率为38.7%,涉及药品包含胺碘酮、银杏叶提取物、氟康唑、伏立康唑、奥希替尼。结论利伐沙班PK-DDI涉及多种药品,主要靶点为P-gp和CYP3A4。肾功能不全患者服用利伐沙班时,联用P-gp和/或CYP3A4抑制剂增加出血风险。利伐沙班应避免与银杏叶提取物、伏立康唑联用。利伐沙班与胺碘酮、氟康唑、奥希替尼联用需严密监测,如凝血酶原时间、抗凝血(Xa)因子水平或利伐沙班血药浓度。
基金Supported by the Vietnam National Foundation for Science and Technology Development,No.NAFOSTED 04/2020/TN.
文摘BACKGROUND Tacrolimus(TAC)is metabolized primarily by the CYP3A-encoded enzyme family(CYP3A4,CYP3A5,and CYP3A7).Individuals expressing the CYP3A51 allele are considered fast metabolizers and generally require higher TAC doses to reach therapeutic levels.AIM To evaluate the predictive value of the TAC concentration-to-dose(C0/D)ratio for identifying CYP3A5 poly-morphisms in renal transplant recipients.METHODS Eighty-six de novo kidney transplant recipients with TAC-based immunosuppression from the Department of Nephrology and Dialysis at Military Hospital 103(Hanoi,Vietnam)were included in this retrospective study.Blood samples were collected within the first week post-transplantation to monitor TAC levels and to perform genotyping for CYP3A5 genetic polymorphisms.RESULTS The CYP3A53/3 genotype was identified in 37 patients(43%),CYP3A51/3 in 40 patients(46.5%),and CYP3A51/1 in 9 patients(10.5%).Patients carrying the CYP3A51/3 or CYP3A51/1 genotype,classified as fast metabolizers(CYP3A5 expressers),had significantly lower TAC C0 concentrations and C0/D ratios compared to slow meta-bolizers(CYP3A53/3 genotype)at multiple time points during follow-up(all P<0.001).Notably,the TAC C0/D ratio obtained on day 1(0.91)was shown to predict CYP3A5 polymorphism with a sensitivity of 84.6%and a specificity of 84.6%.CONCLUSION This study demonstrates that the TAC C0/D ratio provides a reliable predictive value for CYP3A5 polymorphisms,which can be used to individualize TAC dosing in renal transplant recipients in Vietnam and other low-income countries.
