Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses
Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses
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DOI：
10.1177/00912700122010744
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发表时间：
2001-08-01
影响因子：
2.9
通讯作者：
Pumford, NR
中科院分区：
文献类型：
--
作者：
James, LP;Farrar, HC;Pumford, NR
扑热息痛-蛋白质加合物是实验动物服用有毒剂量的扑热息痛后，肝脏小叶中心区出现的扑热息痛毒性的生物标志物。这些生物标志物对扑热息痛诱导的肝损伤具有高度的特异性，并与肝脏转氨酶升高相关。这项前瞻性多中心研究的目的是评价醋氨酚蛋白加合物测定在儿童醋氨酚过量患者中的临床应用。对51例对乙酰氨基酚过量的儿童青少年在常规采血时采集血清标本进行临床监测。6名受试者出现“严重”肝毒性(转氨酶升高1000IU/L)，6名受试者转氨酶升高100~1000IU/L，仅1名受试者血清中检测到对乙酰氨基酚蛋白加合物，1名转氨酶显著升高(6000IU/L)且按Rumack标准有发生肝毒性的高风险患者。虽然这项研究进一步支持了醋氨酚过量后人体内发生了对乙酰氨基酚与肝脏蛋白的共价结合，但用目前的方法检测血清中的对乙酰氨基酚-蛋白质加合物需要肝细胞损伤的重要生化证据。(C)2001年美国临床药理学会。
Acetaminophen-protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen-induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen-protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time of routine blood sampling for clinical monitoring. Six subjects developed "severe" hepatotoxicity (transaminase elevation > 1000 IU/L), and 6 subjects had transaminase elevation of 100 to 1000 IU/L. Acetaminophen-protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6000 IU/L) and high risk for the development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen-protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury. (C) 2001 the American College of Clinical Pharmacology.