皖南地区CYP2C19基因多态性对PCI术后氯吡格雷抗血小板聚集的影响

目的：研究皖南地区CYP2C19基因型分布及其多态性对PCI术后患者氯吡格雷临床疗效的影响。方法：选取我院2017年7月至2017年10月行冠脉造影检查和PCI术治疗的患者100例,采用荧光染色原位杂交技术检测CYP2C19基因型,采用TEG血栓弹力图仪检测血小板聚集抑制率,比较CYP2C19不同基因型及相关指标对血小板聚集抑制率、氯吡格雷抵抗的影响。结果及结论：结果表明,CYP2C19弱代谢型是氯吡格雷抵抗的独立危险因素。氯吡格雷抵抗与CYP2C19弱代谢型相关。     

缺血性脑卒中患者CYP2C19基因代谢型、联用药物与氯吡格雷抵抗关系的研究

目的 探讨CYP2C19基因代谢型、联用药物与氯吡格雷抵抗的关系.方法 选择缺血性脑卒中患者102例,连续口服氯吡格雷75 mg/d,共7d.检测患者CYP2C19各基因型及血小板聚集率,以1年内发生缺血性脑卒中复发终点事件为观察指标.结果 CYP2C19基因弱代谢型15例,中间代谢型39例,强代谢型48例,氯吡格雷抵抗发生率在弱代谢型较中间代谢型高,中间代谢型较强代谢型发生率高,差异均有统计学意义(P＜0.05);氯吡格雷联用阿司匹林、他汀类药可明显减少卒中复发事件(P＜0.05).结论 采用基因分型法可预测缺血性脑卒中患者氯吡格雷疗效,指导临床个体化给药.氯吡格雷联用阿司匹林、他汀类药的应用效果较好.     

CYP2C19基因多态性及患者主要临床资料与氯吡格雷药物抵抗的相关性研究

目的观察药物代谢酶系统中CYP2C19基因多态性及患者主要临床资料与服用氯吡格雷前后血小板聚集率变化(氯吡格雷药物抵抗)的相关性。方法入选拟行冠脉造影检查或支架植入治疗患者35例,根据围手术期应用氯吡格雷前后血小板聚集率变化,将患者分为氯吡格雷抵抗组和非抵抗组。检测CYP2C19基因型,并记录患者年龄、性别、烟酒史、高血压、糖尿病等主要临床资料,分析基因水平及临床水平各因素对血小板聚集及氯吡格雷药物抵抗的影响。结果检测出氯吡格雷抵抗的患者15例,CYP2C19慢代谢基因型患者4例,Logistic回归分析显示,CYP2C19基因型是氯吡格雷抵抗的危险因素(OR=1.236,95%CI:0.273~5.599,P=0.049)。结论 CYP2C19基因型在基因水平与氯吡格雷抵抗相关,临床水平资料未见明显相关性。     

CYP2C19和ABCB1基因检测指导患者氯吡格雷个体化给药

目的利用CYP2C19和ABCB1基因检测结果指导患者氯吡格雷个体化用药。方法选取某院2018年8月~2019年6月30例使用氯吡格雷的患者,采用荧光原位杂交法检测患者氯吡格雷相关基因(CYP2C19*17、CYP2C19*3、CYP2C19*2和ABCB1)的基因型,根据检测结果为患者提供给药建议。另选取1例冠状动脉粥样硬化心脏病PCI术后患者,测定氯吡格雷相关基因型,为患者提供个体化给药建议。结果CYP2C19基因检测结果显示,30例患者中1例为超快代谢型,8例为快代谢型,18例为中间代谢型,3例为慢代谢型;ABCB1 CC野生型13例,CT突变杂合型14例,TT突变纯合型3例。1例冠状动脉粥样硬化心脏病患者PCI术后规律双联抗血小板治疗仍反复胸闷胸痛,CYP2C19基因检测为CYP2C19*1/*2中间代谢型,无ABCB1突变,药物代谢减慢,建议氯吡格雷更换为替格瑞洛。结论通过基因检测指导患者氯吡格雷个体化给药,促进临床合理用药。     

缺血性脑卒中患者CYP2C19基因多态性与个体化用药的相关性

目的:探讨根据CYP2C19代谢分型进行的个体化用药调整对于氯吡格雷治疗缺血性脑卒中的指导作用,为临床个体化用药提供参考。方法:纳入80例脑梗死患者,根据是否行CYP2C19基因检测分为经基因检测的个体化用药指导组40例和非基因检测的对照组40例。个体化用药指导组根据CYP2C19代谢分为:慢代谢型、中间代谢型、快代谢型及超快代谢型。快代谢型及超快代谢型按照常规使用氯吡格雷75 mg,每天1次。中间代谢型采用双倍氯吡格雷剂量150 mg,每天1次。慢代谢型患者氯吡格雷更换为替格瑞洛90 mg,每天2次或停用氯吡格雷,改用阿司匹林肠溶片100 mg每天1次;对照组按照常规使用氯吡格雷75 mg,每天1次。对所有入组患者出院后进行为期3个月的门诊或电话随访。比较两组血管事件发生率和改良Rankin量表(mRS)(0-1)发生率。结果:个体化用药指导组血管事件发生率明显低于对照组,mRS评分(0-1)发生率明显高于对照组,差异均有统计学意义(P<0.05)。结论:经CYP2C19基因检测对缺血性脑卒中患者进行的个体化用药,能显著降低血管不良事件发生率,同时对于患者预后生活能力改善也有显著提高。     

CYP2C19基因多态性与脑梗死患者氯吡格雷反应性的关系

目的:研究脑梗死患者CYP2C19基因多态性与氯吡格雷反应性的关系.方法:收集某院服用氯吡格雷进行抗血小板治疗的急性脑梗死患者232例,采用荧光原位杂交分析法检测其CYP2C19基因型,分为快代谢型(EM)90例、中间代谢型(IM)95例和慢代谢型(PM)47例;采用血栓弹力图测定血小板抑制率,根据血小板抑制率将患者分...     

氯吡格雷对冠心病患者PCI术后CYP2C19、PON1 基因多态性与FIB、D-二聚体水平的相关性研究

目的：分析冠心病患者经皮冠状动脉介入治疗(PCI)术后,规律服用氯吡格雷治疗时CYP2C19、PON1基因多态性与血浆纤维蛋白原（FIB）、D-二聚体水平的相关性研究。方法：选取在某三甲医院确诊为冠心病且行PCI术的患者217例,对217例患者行CYP2C19*2、CYP2C19*3、CYP2C19*17、PON1基因监测,观察患者在规律服用氯吡格雷治疗（75 mg·d-1）1个月以上的血浆FIB、D-二聚体指标。结果：在217名患者中CYP2C19* 17基因未检测出突变型等位基因,因此对超快代谢型基因不做统计分析。CYP2C19基因的快代谢型、中间代谢型、慢代谢型之间的FIB指标对比均无统计学差异（P>0.05）;快代谢型与中间代谢型、快代谢性与慢代谢型之间的D-二聚体指标均无统计学差异（P>0.05）;中间代谢型与慢代谢型之间D-二聚体指标有统计学差异（P<0.05）。PON1基因GG型与GA型、GG型与AA型、GA型与AA型的FIB和D-二聚体指标水平均无统计学差异（P>0.05）。结论：携带CYP2C19慢代谢基因型的患者使用常规氯吡格雷剂量治疗,增加血栓风险,可考虑适当增加氯吡格雷服药剂量或改服替格瑞洛进行溶栓治疗。PON1基因多态性与氯吡格雷治疗血小板反应性差异并无关联性。     

氯吡格雷与质子泵抑制剂是非曲折的这些年

氯吡格雷是噻吩类血小板聚集抑制剂。氯吡格雷本身不具有抗血小板活性,但它能通过在肝脏内的CYP450酶系（主要是CYP2C19）氧化水解成活性代谢产物产生抗血小板作用。而质子泵抑制剂（PPIs）在肝脏中氧化代谢也是由CYP450酶系（主要是CYP2C19、CYP3A4）催化。由于二者代谢都通过CYP2C19酶,所以理论上同时使用氯吡格雷和PPIs会产生竞争性抑制。     

CYP2C19*1、*2基因多态性与氯吡格雷抵抗相关性的系统评价

目的:系统评价CYP2C19*1、*2基因型心血管疾病患者对服用氯吡格雷临床疗效的影响。方法:电子检索PubMed、EBSCO、EMbase、Cochrane library、CNKI、万方中文期刊数据库及维普期刊数据库(VIP),再辅以手工检索,查找有关携带CYP2C19*1、*2基因的心血管疾病患者与氯吡格雷疗效关系的临床对照试验和观察性研究,检索时限为建库至2016年12月。由2名研究者根据纳入与排除标准独立筛选文献、质量评价及数据提取,采用RevMan 5.0软件进行Meta分析。结果:纳入5篇研究,共4544例心血管疾病患者。Meta分析结果显示:心血管疾病患者服用氯吡格雷后,CYP2C19*1和CYP2C19*2基因携带患者植入支架后血栓再形成发生率有显著差异[P=0.000 2,RR=2.46,95%CI(1.54,3.92)],其CYP2C19*2基因型携带者较CYP2C19*1型可明显增加血栓形成,但2组在心血管事件发生率上差异不显著(P>0.05)。结论:在服用氯吡格雷的心血管患者中,CYP2C19*2基因型较CYP2C19*1基因型更易发生支架后血栓,但心血管时间发生率未见明显差异,鉴于CYP2C19*2基因型携带患者发生植入支架后血栓再形成风险增加,建议在拟行PCI手术并使用氯吡格雷的患者应先测定CYP2C19*2基因型,再考虑是否应用氯吡格雷抗血小板治疗。     

CYP2C19、ABCB1和PON1基因多态性与氯吡格雷抑制血小板聚集作用的相关性研究

目的:探讨CYP2C19、ABCB1和PON1基因多态性与氯吡格雷抑制血小板聚集作用的相关性。方法:纳入诊断为急性缺血性脑卒中或接受经皮冠状动脉介入术(PCI)后服用氯吡格雷和阿司匹林治疗的患者59例,测定CYP2C19(rs4244285、rs4986893)、ABCB1(rs1045642)和PON1(rs662)基因型及血栓弹力图(TEG),并对患者进行1年的随访,记录临床终点事件。应用单因素和多因素回归,分析患者CYP2C19、ABCB1、PON1基因型、一般情况及临床因素对氯吡格雷抑制血小板聚集作用的影响,比较不同基因型患者的氯吡格雷疗效。结果:59例患者中氯吡格雷治疗相关的血小板高反应性(HTPR)的发生率为8.5%。CYP2C19快代谢型、中间代谢型和慢代谢型患者血小板抑制率分别为(86.0±10.1)%、(78.4±17.3)%和(66.4±23.0)%,快代谢型和慢代谢型之间血小板抑制率差异有显著性(P=0.047),ABCB1和PON1各基因型之间血小板抑制率的差异无显著性(P>0.05),全变量多因素logistic回归分析未发现CYP2C19、ABCB1、PON1基因型与HTPR相关(P=0.681)。随访1年中,CYP2C19快代谢型、中间代谢型、慢代谢型患者的临床事件分别有2、3和3例;ABCB1携带TT、TC、CC等位基因患者的临床事件分别有1,3和4例;PON1携带AA、AG、GG等位基因患者的临床事件分别有4,2和2例,各基因型之间患者临床终点事件差异无显著性(P>0.05)。结论:根据CYP2C19、ABCB1和PON1基因多态性尚不能预测服用氯吡格雷后的临床疗效。     

CYP2C19基因多态性对奥美拉唑治疗儿童幽门螺旋杆菌疗效的影响

目的：探索儿童CYP2C19的基因分布,以及基因多态性对奥美拉唑治疗儿童幽门螺旋杆菌疗效的影响。方法：收集本院消化科住院治疗的111例幽门螺旋杆菌阳性患儿血样,采用数字荧光杂交测定CYP2C19的基因型,根据结果分为4种代谢类型：超快代谢型（UM）、快代谢型（EM）、中间代谢性（IM）以及慢代谢型（PM）,统计不同基因型、代谢型分布频率。常规奥美拉唑剂量下[0.6~1 mg·（kg·d）^-1（最大量40 mg·d^-1）],比较不同代谢型患儿幽门螺旋杆菌根除率。快代谢组患儿,比较奥美拉唑常规剂量组和高剂量组[1.2~2 mg·（kg·d）^-1（最大量80 mg·d^-1）]的根除率。结果：CYP2C19*1、CYP2C19*2、CYP2C19*3和CYP2C19*17等位基因频率分别为67.12%,24.77%,6.76%和1.35%。UM型、EM型、IM型以及PM型代谢组分布频率分别为0.9%,50.45%,34.23%,14.41%。常规奥美拉唑剂量下,EM组根除率（53.57%）显著低于IM（78.95%）及PM组（87.5%）。快代谢组患儿,高剂量组根除率（82.14%）显著高于常规剂量组（53.57%）。结论：剂量相同的条件下,EM组的根除率更低,但增加剂量可以提高EM组的根除率,这可用于指导临床个体化用药。通过基因检测,可以选择更合适的药物剂量。     

Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are mainly metabolized by CYP2C19 in the liver. There are genetically determined differences in the activity of this enzyme. The genotypes of CYP2C19 are classified into the three groups, rapid extensive metabolizer (RM), intermediate metabolizer (IM), and poor metabolizer (PM). The pharmacokinetics and pharmacodynamics of PPIs depend on CYP2C19 genotype status. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs influence the cure rates for the gastro-esophageal reflux disease and H. pylori infection by PPI-based therapies. For the better PPI-based treatment, doses and dosing schemes of PPIs should be optimized based on CYP2C19 genotype status.     

CYP2C19 pharmacogenomics associated with therapy of Helicobacter pylori infection and gastro-esophageal reflux diseases with a proton pump inhibitor

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are metabolized by CYP2C19 in the liver. There are genetic differences in the activity of this enzyme. Genotypes of CYP2C19 are classified into three groups, rapid metabolizer (RM: *1/*1), intermediate metabolizer (IM: *1/*X) and poor metabolizer (PM: *X/*X) (*1 and 'X' represent the wild-type and mutant allele, respectively). The pharmacokinetics and pharmacodynamics of PPIs differ among three different CYP2C19 genotype groups. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotypic differences in pharmacokinetics and pharmacodynamics of PPIs influence the healing and eradication rates for the gastro-esophageal reflux disease and Helicobacter pylori infection by PPI-based regimens. Recently, the CYP2C19 genotype-based tailored therapy for H. pylori infection has been found to be effective. CYP2C19 pharmacogenetics should be taken into consideration for the personalization of a PPI-based therapy.     

Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans

Several recent in-vitro data have revealed that CYP2C19, in addition to CYP2C9, is also involved in the 4-methylhydroxylation of tolbutamide. We evaluated the relative contribution of CYP2C9 and CYP2C19 genetic polymorphisms on the disposition of blood glucose lowering response to tolbutamide in normal healthy Korean subjects in order to reappraise tolbutamide as a selective in-vivo probe substrate of CYP2C9 activity. A single oral dose of tolbutamide (500 mg) or placebo was administered to 18 subjects in a single-blind, randomized, crossover study with a 2-week washout period. Twelve subjects (of whom six were CYP2C19 extensive metabolizer (EM) and six were CYP2C19 poor metabolizer (PM) genotype) were of the homozygous wild-type CYP2C9*1 genotype; the other six subjects were of the CYP2C9*1/*3 and CYP2C19 EM genotype. Pharmacokinetic parameters were estimated from plasma and urine concentrations of tolbutamide and 4-hydroxytolbutamide. Serum glucose concentrations were measured before and after oral intake of 100 g dextrose. In subjects heterozygous for the CYP2C9*3 allele, C(max) and AUC of tolbutamide were significantly greater and the plasma half-life significantly longer than those in homozygous CYP2C9*1 subjects. No pharmacokinetic differences were found between CYP2C19 EM and PM genotype subjects. The estimated AUC of the increase in serum glucose after oral intake of 100 g dextrose was 2.7-fold higher in subjects with the wild-type CYP2C9 genotype than in those with CYP2C9*1/*3, but CYP2C19 genetic polymorphism did not alter the blood glucose lowering effect of tolbutamide. The plasma AUC of 4-hydroxytolbutamide and the ratio of 4-hydroxytolbutamide/tolbutamide did not differ significantly between CYP2C19 PM and EM genotype subjects, while these parameters were about twice as high in subjects with the wild-type CYP2C9 genotype than in heterozygous CYP2C9*3 subjects (P < 0.05). Our results strongly suggest that the disposition and hypoglycemic effect of tolbutamide are affected mainly by CYP2C9 genetic polymorphism, but not by CYP2C19 polymorphism. The in-vivo contribution of CYP2C19 to tolbutamide 4-methylhydroxylation appears to be minor in humans. This suggests that, at least in vivo, tolbutamide remains a selective probe for measuring CYP2C9 activity in humans.     

Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes

BACKGROUND: S-mephenytoin 4'-hydroxylase (CYP2C19) catalyses the metabolism of rabeprazole to some extent. Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole, rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19-related genetic polymorphism. AIM: To determine whether the pharmacodynamic effects of rabeprazole on intragastric pH and serum gastrin levels, and its pharmacokinetics depend on the CYP2C19 genotype status. METHODS: Eighteen healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. They consisted of six each of homozygous extensive metabolisers (homo EMs), heterozygous extensive metabolisers (hetero EMs), and poor metabolisers (PMs). Helicobacter pylori status was determined by serology. After a single oral dose of 10 mg or 20 mg rabeprazole or water only (baseline data), intragastric pH values were monitored for 24 h. Plasma levels of rabeprazole and serum gastrin were also measured for 24 h post-dose. RESULTS: Five homo EM, six hetero EM and four PM subjects were H. pylori-negative. After rabeprazole administration, significant differences in intragastric mean pH values, serum gastrin AUC(0-24) and plasma levels of rabeprazole were observed among the three different genotype groups. CONCLUSION: The pharmacodynamic effects of rabeprazole and its pharmacokinetics depend on the CYP2C19 genotype status.     

Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status.

Diazepam is metabolized by CYP2C19 and CYP3A4 in the liver. CYP2C19 shows genetic polymorphism associated with the poor metabolizer (PM) and extensive metabolizer (EM) phenotypes. The aim of this study was to assess the effect of diltiazem, a CYP3A4 inhibitor, on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Thirteen healthy volunteers (eight EMs and five PMs) were given placebo or diltiazem (200 mg) orally for 3 days before and for 7 days after the oral 2-mg dose of diazepam in a double-blind, randomized, crossover manner. The pharmacokinetics and pharmacodynamics of diazepam were assessed with and without diltiazem. Plasma concentrations and area under the plasma concentration-time curves (AUCs) of diazepam and N-desmethyldiazepam were significantly greater in the PM compared with the EM group during the placebo phase. Diltiazem significantly increased AUC and prolonged elimination t(1/2) of diazepam in both the PM and EM groups. These pharmacokinetic changes, however, caused no significant difference in the pharmacodynamics between the two trial phases. Diltiazem affects the pharmacokinetics of diazepam in the PM and EM groups of CYP2C19. Inhibition of CYP3A4 by a concomitant substrate drug like diltiazem may cause a pharmacokinetic interaction with diazepam irrespective of CYP2C19 genotype status, but whether this interaction would reflect a pharmacodynamic change of diazepam remains unconfirmed by our study.     

Genetic polymorphisms of CYP2C19 influences the response to clopidogrel in ischemic heart disease patients in the South Indian Tamilian population

Background

The antiplatelet activity of clopidogrel is variable among patients suffering from ischemic heart disease. Variation in the cytochrome P450 2C19 (CYP2C19) gene coding for the CYP2C19 enzyme is one of the major determinants of this variable response to clopidogrel. The activity of the CYP2C19 enzyme, which plays a role in the conversion of the prodrug clopidogrel to its active metabolite, is genetically influenced by polymorphisms in its gene. The aim of our study was to evaluate the association of CYP2C19 polymorphisms and the antiplatelet effect of clopidogrel in the South Indian Tamilian population.

Materials and methods

Genotyping and platelet aggregation results of 149 ischemic heart disease patients on clopidogrel maintenance therapy (75 mg daily dose) were analyzed in this study. CYP2C19 polymorphisms were genotyped by the PCR-restriction fragment length polymorphism method. We measured residual platelet activities in these patients on clopidogrel therapy in terms of impedance (expressed as ohms). The study subjects were divided into two metabolizer phenotype groups [group 1: poor/intermediate metabolizers (PM/IM); group 2: extensive/ultra-rapid metabolizers (EM/URM)] based on CYP2C19 genotype, and the residual platelet activities were compared. Higher values of impedance denote increased residual platelet activity.

Results

Poor/intermediate metabolizers had significantly higher impedance values than EM/URM [(median; range) 4.0; 0–13 vs. 2.0; 0–11, respectively; p?=?0.04]. These higher impedance values denote higher residual platelet activities among the carriers of loss-of-function alleles (CYP2C19*2,*3) than among non-carriers. However, residual platelet activities were lower among the carriers of the gain-of-function allele (CYP2C19*17) than among non-carriers, although this difference was not significant.

Conclusion

Patients with CYP2C19 (*2 or *3) genetic polymorphisms had higher residual platelet activities and were associated with a reduced antiplatelet response to clopidogrel. As the South Indian Tamilian population is characterized with higher frequencies of these genetic polymorphisms, our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy.     

伏立康唑治疗慢性肺曲霉病患者CYP2C19基因多态性的检测及其意义

目的研究CYP2C19基因多态性对伏立康唑治疗慢性肺曲霉病(CPA)患者的影响,为慢性肺曲霉病的个体化用药提供参考。方法选取2019年1~10月在我院肺结核科住院并确诊为慢性肺曲霉病的80例患者作为研究对象,80例患者均使用伏立康唑抗真菌治疗。按照有无检测CYP2C19基因多态性分为试验组(n=40)及对照组(n=40)。试验组患者按照基因检测的结果调整用药方案,对照组则按照伏立康唑的常规剂量给药(4 mg·kg^-1,q12h)。比较两组患者间及不同代谢型患者间的不良反应及治疗效果。结果试验组40例患者分析了3个基因位点(CYP2C19*2,CYP2C19*3,CYP2C19*17),共检出快代谢型(extensive metabolizer,EM)14例(35.00%),中间代谢型(intermediate metabolizer,IM)18例(45.0%),慢代谢型(poor metabolizer,PM)8例(20.0%)。IM组及PM组的不良反应率比EM组高(P<0.05)。而治疗有效率,PM组高于IM组,IM组高于EM组,试验组的有效率对比对照组高(P>0.05),发生不良反应率低。结论CYP2C19基因多态性检测可用于指导伏立康唑治疗慢性肺曲霉病患者,提高安全性及有效性。     

肠道菌群对硫酸氢氯吡格雷及其活性代谢产物在大鼠体内药动学的影响

目的：探究肠道菌群变化对硫酸氢氯吡格雷及其活性代谢产物在大鼠体内药动学的影响。方法：24只健康大鼠随机分为益生菌组、抗生素组和对照组,每组8只,分别灌胃双歧杆菌乳杆菌三联活菌（0.8 g·kg^-1）、阿莫西林克拉维酸钾片（125 mg·kg^-1）和等体积的纯化水,连续7 d。第8天给予硫酸氢氯吡格雷片,并于给药前和给药后不同时间点取血于含有衍生试剂的抗凝管中,LC-MS/MS法测定血药浓度,绘制药时曲线,使用DAS 2.1.1拟合药动学参数,SPSS 21.0进行统计学比较。结果：益生菌组、抗生素组和对照组硫酸氢氯吡格雷和活性代谢产物衍生物（CAMD）的主要药动学参数AUC_0-t、AUC_0-∞、t_1/2、t_max、CL、V、C_max均没有统计学差异（P>0.05）。结论：肠道菌群变化对硫酸氢氯吡格雷及其活性代谢产物的药动学参数没有影响。     

CYP2D6基因多态性对美托洛尔疗效影响的meta分析

目的 评价细胞色素P450 2D6（CYP2D6）药物代谢酶基因多态性对美托洛尔药物疗效的影响。方法 从各数据库（中国知网、维普、万方、SCIE、PubMed、Embase）检索从建库至2019年7月发表的关于CYP2D6与美托洛尔研究的文献,筛选并纳入文献进入质量评价,提取文献数据,对所有纳入文献结局指标使用RevMan 5.3进行定量meta分析。结果 共纳入文献8篇,其中具有酶活性代谢组（non-poor metabolizer,non-PM）631例,弱代谢组（poor metabolizer,PM）206例。PM组的收缩压（systolic blood pressure,SBP）降幅较non-PM组大,两者无明显差异（P=0.20）。non-PM组内比较,中速代谢组（intermediate metabolizer,IM）SBP的降幅大于强代谢组（extensive metabolizer,EM）,差异有统计学意义（P=0.03）。PM组舒张压（diastolic blood pressure,DBP）的降幅大于non-PM组,差异有统计学意义（P=0.01）,IM组的DBP降幅大于EM组,差异有统计学意义（P=0.02）。non-PM组心率（heart rate,HR）降幅大于PM组,差异有统计学意义（P=0.05）,IM组HR降幅大于EM组（P=0.002）。结论 meta分析结果显示,PM组的降压效果优于non-PM各组（UM、EM及IM组）,主要是在降DBP方面,而控制HR的疗效弱于non-PM各组。