摘要
目的:研究肾移植术后患者CYP3A5*3基因多态性对他克莫司(FK506)血药浓度/剂量比(C/D)及急性排斥反应和不良反应的影响。方法:采用聚合酶链反应(PCR)和限制性内切片段长度多态性(RFLP)的方法检测肾移植患者CYP3A5*3基因型,比较不同基因型患者之间FK506的C/D值以及急性排斥反应(AR)、不良反应的差异。结果:肾移植术后1个月内,*3/*3型患者FK506的C/D值为151.7±60.0,显著高于*1/*1型和*1/*3型患者的72.6±21.7和99.4±40.3(P<0.01);移植术后3个月内*1/*1型患者AR的发生率为25.0%,显著高于*1/*3型和*3/*3型患者的10.8%和8.8%(P<0.05);而术后肝功能异常、高血糖、药物肾毒性等不良反应发生率*1/*3型和*3/*3型显著高于*1/*1型患者(P<0.05)。结论:CYP3A5*3基因多态性与肾移植患者FK506的C/D值及急性排斥反应(AR)、不良反应密切相关。
OBJECTIVE To investigate the impact of CYP3A5 ＊3 genetic polymorphism on the eoncentration/dose（C/D）ratio, acute rejection and adverse reaction of tacrolimus（FKS06） in the renal patients after transplantation. METHODS The CYP3A5 ＊ 3 genotype was determined by PCR-RFLP method. The differences of C/D ratio, acute rejection and adverse reaction were compared among all of the genotype groups treated with FKS06. RESULTS During the first month after transplantation, the C/D ratio of FK506 in patients with ＊ 3/＊ 3 genotype group was 151.7 ±60. 0, which was higher than 72. 6 ±21.7 and 99.4±40.3 of ＊1/＊ 1 and ＊ 1/＊ 3 genotype groups（P〈0.01）. The ratio of acute rejection in ＊ 1/＊ 1 group was 25.0%, which was higher than 10. 8% and 8. 8% of ＊ 1/＊ 3 and ＊ 3/＊ 3 groups within 3 months（P〈0. 05）. The ratio of adverse reaction about dysfunction of liver, hyperglycosemia and neurotoxicity was significantly increased in ＊ 1/＊ 3 and ＊3/＊ 3 group compared with ＊ 1/＊ 1 group （P〈0. 05）. CONCLUSION There was intimate relation between the C/D ratio of FK506, acute rejection and adverse reaction and CYP3A5 ＊ 3 genetic polymorphism in the transplant patients.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2010年第4期313-316,共4页
Chinese Journal of Hospital Pharmacy
