摘要
目的比较他克莫司(FK506)治疗FK506不同代谢型重症肌无力(MG)患者的疗效、有效血药浓度、有效剂量及安全性的差异,并初步探讨CYP3A5基因多态性在指导MG个体化治疗中的作用。方法收集MG患者32例,行CYP3A5*3A6986G等位基因多态性检测,AA型及AG型归为快代谢型组,GG型为慢代谢型组。均给予FK506 0.5～1mg/d口服,逐渐加量,每天记录患者绝对评分,当与治疗前相比绝对评分减少大于50%时,为治疗达标,记录当时的剂量、总服药天数及血药浓度。结果达标时快代谢组的平均血药浓度/剂量(C/D)明显低于慢代谢组(P<0.01),当时口服的FK506剂量/体重也明显大于慢代谢组(P<0.01),达标时间也明显长于慢代谢组(P<0.05),治疗期间共出现3例(9.4%)轻度不良反应。结论 FK506治疗不同CYP3A5*3基因型MG患者的起效时间、有效剂量、有效血药浓度均不同;CYP3A5基因多态性检查在FK506个体化治疗MG中具有一定指导意义。
Objective To compare the difference of the effect, effective blood drug level, effective dosage and safety of tacrolimus （FKS06） treating the patients with myasthenia gravis （MG） between two FK506 metabolic patterns, and preliminarily find the value of CYP3A5 polymorphism in guiding individualized treatment of MG. Methods We detected CYP3A5 ＊ 3 A6986G polymorphism in 32 MG patients. AA and AG were the fast metabolic pattern while GG was the slow metabolic pattern. All patients were treated with FKS06 at the initial dosage of 0.5-1 mg/d. Then the dosage increased gradually and the absolute scores of the MG patients were recorded every day. When the scores gradually decreased 50% or more comparing with the scores before treatment, it is regarded as achieving the treatment target. The dosage, duration of treatment, and blood FKS06 concentration were recorded at that day. Results The patients of fast metabolic pattern had a lower concentration per dosage （C/D） （P〈0.01）, a higher dosage per weight （P〈0.01） and a longer duration of treatment （P〈 0.05） compared with the patients of slow metabolic pattern. Mild adverse reaction occured in 3 cases （9.4%） during the treatment. Conclusions The time of improvement, effective dosage, and effective drug concentrations are different in patients with different CYP3A5 genotypes treated with FKS06. Detection of CYP3A5 polymorphism has some guidance to individualized treatment of FKS06 in patients with MG.
出处
《中国神经免疫学和神经病学杂志》
CAS
北大核心
2013年第1期17-19,23,共4页
Chinese Journal of Neuroimmunology and Neurology
