多奈哌齐血药浓度及其代谢酶CYP3A4基因多态性在轻中度Alzheimer's病治疗中的应用

Application of Donepezil plasma concentration and its metabolic enzyme CYP3A4 gene polymorphism in the treatment of mild to moderate Alzheimer’s disease

目的探讨多奈哌齐(DNP)治疗轻中度Alzheimer’s病(AD)患者的有效血药浓度及代谢酶CYP3A4基因多态性对DNP血药浓度的影响。方法对70例首诊的轻中度AD患者进行MMSE测评,随后予DNP治疗。服药6月后进行DNP血药浓度及代谢酶CYP3A4基因多态性检测,并行MMSE量表复评和临床印象变化量表(CIBIC-plus)评定。根据量表结果确定有效组,分析其DNP血药浓度和CYP3A4基因多态性,探讨DNP治疗AD的有效血药浓度及CYP3A4基因多态性对DNP血药浓度的影响。结果有效组中,患者DNP平均血药浓度为(52.17±7.13)ng/ml,其中服药5 mg患者平均血药浓度为(47.63±8.13)ng/ml,服药10 mg患者平均血药浓度为(52.80±6.85)ng/ml。携带等位基因CYP3A4*18B-G和/或CYP3A4*1G-T者的DNP血药浓度高于未携带者,在服药10 mg组中差异更显著。结论DNP治疗轻中度AD的有效血药浓度为45~59 ng/ml;CYP3A4基因多态性影响DNP血药浓度。血药浓度监测和CYP3A4基因多态性检测为指导AD患者DNP个体化治疗提供参考。

Objective To explore the effective plasma concentration of donepezil(DNP)and related metabolic enzyme CYP3A4 gene polymorphisms in DNP plasma concentration in the treatment of mild to moderate Alzheimer’s disease(AD)patients.Methods Seventy patients with first diagnosis of mild to moderate AD were assessed with MMSE and then treated with DNP.After 6 months of treatment,DNP plasma concentration and CYP3A4 gene polymorphism were detected;MMSE and Impression of Change-Plus(CIBIC-plus)were evaluated.According to the results of the scale,the effective group were determined and its plasma concentration of DNP and CYP3A4 gene polymorphism were analyzed.The effective plasma concentration of DNP in the treatment of AD and the influence of CYP3A4 gene polymorphism on the plasma concentration of DNP were explored.Results The DNP plasma concentration in the effective group was(52.17±7.13)ng/ml,which the plasma concentration of 5 mg was(47.63±8.13)ng/ml,the plasma concentration of 10 mg was(52.80±6.85)ng/ml.The DNP plasma concentrations of CYP3A4*18B-G allele and/or CYP3A4*1G-T allele carriers were higher than those of non-carriers,the difference was more significant when taking 10 mg.Conclusions The effective plasma concentration of DNP in the treatment of mild to moderate AD is 45-59 ng/ml;CYP3A4 gene polymorphism affects the plasma concentration of DNP.The monitoring of DNP plasma concentration and detection of CYP3A4 gene polymorphism can provide reference for guiding the individualized treatment in AD patients.