摘要
探讨全身型重症肌无力(MG)患者他克莫司(FK506)治疗血药质量浓度个体差异与CYP3A5基因多态性的关系.收集临床确诊的难治性全身型MG患者36例,均为OssennanⅡB或美国MG基金会(MGFA)ⅢB型,口服FK5061～3 mg.d-1,记录患者体质量、他克莫司使用剂量,LC-MS/MS法检测他克莫司全血质量浓度,并利用PCR-RELP法检测患者CYP3A5*3 A6986G多态性,分析血药质量浓度/剂量比与基因型的关系.结果表明:CYP3A5基因为AA或AG型患者的血药质量浓度/剂量明显低于GG型((44.56±23.21)/(150.14±123.12),P<0.001).可见,在重症肌无力(MG)患者中CYP3A5基因多态性与FK506的血药质量浓度显著相关.根据上述不同患者基因型药物代谢的特点进行剂量调整,或在使用FK506前通过基因型检测更合理地选择患者,有助于提高FK506的临床疗效,减少其副作用.
Correlation between CYP3A5 polymorphism and whole blood tacrolimus（FK506） concentration was investigated in myasthenia gravis patients.Blood samples were collected from 36 cases of definitely diagnosed refractory generalized MG（Osserman ⅡB or MCFA ⅢB） who received FK506（1-3 mg）.Whole blood tacrolimus（FK506） concentration was tested by LC-MS/MS,PCR-RELP was used to determine CYP3A5 genotype.FK506 concentrations standardized by dosage and body weight（FK506 concentration per dose/kg） were compared among 3 subgroups within CYP3A5.Of the 36 patients 2（5.6%）,15（41.7%）,and 19（52.7%） were carriers of AA,AG and GG.The ratio for patients with AA/AG was remarkably lower than those with GG（（44.56±23.21） vs（150.14±123.12）,P〈0.001）.CYP3A5 gene polymorphism is correlated with tacmlimus pharmacokinetics and dose requirements.Based on the above data,genotype detection methods could be employed to help with dose selection for immunosuppressive drugs
出处
《北京师范大学学报（自然科学版）》
CAS
CSCD
北大核心
2010年第4期503-505,共3页
Journal of Beijing Normal University(Natural Science)
