Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin.
Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin.
复制标题
耐药性和伪耐药性：肠涂层阿司匹林的意外结果。
DOI：
10.1161/circulationaha.112.117283
复制
发表时间：
2013-01-22
期刊：
影响因子：
37.8
通讯作者：
FitzGerald GA
中科院分区：
文献类型：
--
作者：
Grosser T;Fries S;Lawson JA;Kapoor SC;Grant GR;FitzGerald GA
小剂量阿司匹林可降低心肌梗死和中风的继发性发病率。对阿司匹林的耐药性可能导致治疗失败。尽管存在这样的担忧，但对“阿司匹林抵抗”的明确定义还没有出现，对其发生率的估计也存在显著差异。我们的目标是确定机制上一致的、稳定的和特定的阿司匹林耐药表型的共性--这可能是由遗传原因解释的。对400名健康志愿者进行了单剂量口服325毫克速释或肠溶阿司匹林的疗效筛选。反应参数反映了阿司匹林的分子靶标环氧合酶-1的活性。有一次出现“阿司匹林抵抗”的患者接受了重复测试，如果仍然“抵抗”，则分别接受小剂量肠溶阿司匹林(81毫克)和氯吡格雷(75毫克)治疗一周。可变吸收导致对单剂量325毫克肠溶阿司匹林(高达49%)的明显抵抗频率很高，但不能立即释放阿司匹林(0%)。所有受试者在重复服用阿司匹林、延长给药后间隔或在体外向其血小板中添加阿司匹林后，均对阿司匹林有效。阿司匹林的药理耐药性很少见；这项研究未能确定一个真正的耐药性病例。假耐药，反映药物吸收延迟和减少，使肠溶阿司匹林给药复杂化，但不能立即释放阿司匹林。临床试验.gov。标识：NCT00948987。
Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of “aspirin resistance” has emerged and estimates of its incidence have varied remarkably. We aimed to determine the commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin – such as might be explained by genetic causes. Healthy volunteers (n=400) were screened for their response to a single oral dose of 325 mg immediate release or enteric coated aspirin. Response parameters reflected the activity of aspirin's molecular target, cyclooxygenase-1. Individuals who appeared “aspirin resistant” on one occasion underwent repeat testing and if still “resistant” were exposed to low dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each. Variable absorption caused a high frequency of apparent resistance to a single dose of 325 mg enteric coated aspirin (up to 49%) but not to immediate release aspirin (0%). All individuals responded to aspirin upon repeated exposure, extension of the post dosing interval or addition of aspirin to their platelets ex vivo. Pharmacological resistance to aspirin is rare; this study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration. clinicaltrials.gov. Identifier: NCT00948987.