Adduct Dipstick for Diagnosis of Acetaminophen Toxicity

用于诊断对乙酰氨基酚毒性的加合物试纸

• 批准号: 8499293
• 负责人: Laura P James
• 金额: $ 56.86万
• 依托单位: ACETAMINOPHEN TOXICITY DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8499293
• 关键词: Accounting; Acetaminophen; Acute; Acute Liver Failure; Amino Acids; Aminophenols; Antibodies; Bedside Testings; Binding; Biological Assay; Biological Markers; Blood; Blood specimen; Cessation of life; Clinical; Clinical Trials; Cysteine; Cytolysis; Detection; Developed Countries; Development; Devices; Diagnosis; Diagnostic; Diagnostic Sensitivity; Diagnostic Specificity; Diagnostic tests; Dose; Drug usage; Etiology; Fever; Freezing; Future; Goals; Grant; Hepatocyte; Hepatology; Hepatotoxicity; High Pressure Liquid Chromatography; Hospitalization; Hour; Human; Imines; Immunoassay; Laboratories; Laboratory Research; Liver; Liver diseases; Measurement; Measures; Mediating; Medical center; Metabolic; Methods; Overdose; Pain; Parents; Patients; Performance; Pharmaceutical Preparations; Phase; Physicians; Plasma; Positioning Attribute; Proteins; Publishing; Reaction; Reagent; Recording of previous events; Reliance; Reporting; Research; Sampling; Serum; Small Business Technology Transfer Research; Specificity; System; Testing; Therapeutic; Time; Toxic effect; Validation; Work; acetaminophen cysteine; acetaminophen overdose; adduct; base; clinically relevant; commercialization; efficacy research; innovation; liver injury; novel diagnostics; p-Benzoquinones; para-benzoquinone; peripheral blood; point-of-care diagnostics; prototype; validation studies

DESCRIPTION (provided by applicant): Acetaminophen (APAP) is the most commonly used drug for the treatment of pain and fever in the world today. In large doses, APAP causes acute liver failure and is the leading cause of acute liver failure in the US. The current laboratory test for the diagnosis of APAP toxicity, measurement of APAP levels in peripheral blood, is only effective in the first 24 hours of APAP overdose. Acetaminophen Toxicity Diagnostics (ATD), LLC has developed a rapid, point-of-care diagnostic assay (dipstick) for the measurement of APAP protein adducts. Adducts are sensitive and specific biomarkers of APAP hepatotoxicity that may be detected in peripheral blood 6 to 7 days after a toxic overdose of APAP. The dipstick detects APAP irreversibly bound to proteins (APAP protein adducts) by using antibodies specific for adducts in the detection system. The dipstick is reliable, accurate and provides rapid results. In Specific Aim 1, the dipstick will be calibrated to detect levels of APAP protein adducts corresponding to severe liver toxicity and 2000 precision manufactured, research use dipsticks will be produced. In Specific Aim 2, the dipsticks will be tested internally for stability, specificity, and diagnostic sensitivity using stored, frozen clinical samples. In Specific Aim 3, six major hepatology centers will participate in a study to measure dipstick performance in patients with acute liver injury and acute liver failure. Successful completion of these aims will establish the clinical utility of the dipstick, an innovation that will enhance the diagnosis of APAP toxicity.

描述（由申请人提供）：对乙酰氨基酚（APAP）是当今世界上最常用的治疗疼痛和发热的药物。在大剂量下，APAP会导致急性肝衰竭，是美国急性肝衰竭的主要原因。目前用于诊断APAP毒性的实验室测试，即测量外周血中的APAP水平，仅在APAP过量的前24小时内有效。对乙酰氨基酚毒性诊断（ATD）有限责任公司开发了一种快速、即时诊断测定（试纸），用于测量APAP蛋白加合物。加合物是APAP肝毒性的敏感和特异性生物标志物，可在毒性过量APAP后6至7天在外周血中检测到。试纸通过使用检测系统中加合物特异性抗体检测与蛋白质（APAP蛋白加合物）不可逆结合的APAP。试纸是可靠的，准确的，并提供快速的结果。在特定目标1中，将校准试纸以检测对应于严重肝毒性的APAP蛋白加合物水平，并将生产2000个精密制造的研究用试纸。在特定目标2中，将使用储存的冷冻临床样本对试纸的稳定性、特异性和诊断灵敏度进行内部检测。在具体目标3中，六个主要的肝病中心将参与一项研究，以测量急性肝损伤和急性肝衰竭患者的试纸性能。这些目标的成功完成将确立试纸的临床实用性，这是一项将增强APAP毒性诊断的创新。