Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose.
Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose.
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DOI：
10.1038/clpt.2008.190
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发表时间：
2008-12
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
对乙酰氨基酚蛋白加合物（APAP加合物）进行了定量分析，157名青少年和儿童在8个儿科医院与APAP过量的主要投诉。其中两名患者需要肝移植，而所有其他患者均自行恢复。APAP加合物峰值与肝转氨酶峰值、N-乙酰半胱氨酸（NAC）治疗时间和Rumack-Matthews列线图确定的风险相关。采用事后经验贝叶斯估计值进行群体药代动力学分析（NONMEM），确定受试者的消除速率常数（ke）、消除半衰期（t1/2）和加合物最大浓度（Cmax）。平均（±SD）ke和半衰期分别为0.486 ± 0.084天-1和1.47 ± 0.30天，Cmax为1.2（±2.92）nmol/ml血清。模型推导的48 h预测加合物值（加合物48）与加合物Cmax、加合物Tmax、Rumack-Matthews风险测定、峰值天冬氨酸转氨酶（AST）和峰值丙氨酸转氨酶（ALT）相关。APAP加合物在APAP过量的儿科和青少年患者中的药代动力学和临床相关性支持进一步检查APAP加合物作为APAP毒性的临床相关和特异性生物标志物的作用的必要性。
Acetaminophen protein adducts (APAP adducts) were quantified in 157 adolescents and children presenting at eight pediatric hospitals with the chief complaint of APAP overdose. Two of the patients required liver transplantation, whereas all the others recovered spontaneously. Peak APAP adducts correlated with peak hepatic transaminase values, time-to-treatment with N-acetylcysteine (NAC), and risk determination per the Rumack–Matthews nomogram. A population pharmacokinetic analysis (NONMEM) was performed with post hoc empiric Bayesian estimates determined for the elimination rate constants (ke), elimination half-lives (t½), and maximum concentration of adducts (Cmax) of the subjects. The mean (±SD) ke and half-life were 0.486 ± 0.084 days−1 and 1.47 ± 0.30 days, respectively, and the Cmax was 1.2 (±2.92) nmol/ml serum. The model-derived, predicted adduct value at 48 h (Adduct 48) correlated with adduct Cmax, adduct Tmax, Rumack–Matthews risk determination, peak aspartate aminotransferase (AST), and peak alanine aminotransferase (ALT). The pharmacokinetics and clinical correlates of APAP adducts in pediatric and adolescent patients with APAP overdose support the need for a further examination of the role of APAP adducts as clinically relevant and specific biomarkers of APAP toxicity.
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影响因子：
3.9
作者：
James, LP;Mayeux, PR;Hinson, JA
通讯作者：
Hinson, JA
影响因子：
6.1
作者：
HINSON, JA;POHL, LR;GILLETTE, JR
通讯作者：
GILLETTE, JR
影响因子：
2.9
作者：
James, LP;Farrar, HC;Pumford, NR
通讯作者：
Pumford, NR
影响因子：
8
作者：
James, Laura P.;Alonso, Estella M.;Squires, Robert H.
通讯作者：
Squires, Robert H.
DOI：
10.1097/00004583-199207000-00016
发表时间：
1992-07-01
影响因子：
13.3
作者：
MYERS, WC;OTTO, TA;MORENO, A
通讯作者：
MORENO, A