Authors: Rothen JP, Haefeli WE, Meyer UA, Todesco L, Wenk M.

作者：Rothen JP, Haefeli WE, Meyer UA, Todesco L, Wenk M.

Journal: Pharmacogenetics, December 1998; Volume 8, Issue 6, Pages 553-9

期刊：药物遗传学，1998年12月；第8卷，第6期，553-9页

DOI: 10.1097/00008571-199812000-00012

Abstract: This study investigates the inhibitory effects of acetaminophen on hepatic N-acetyltransferase 2 (NAT2), an enzyme responsible for the acetylation of various drugs and xenobiotics. The study includes both in vitro and in vivo experiments:

• In Vitro Study: Acetaminophen was found to competitively inhibit NAT2 activity in human liver homogenates. The inhibition constants (Ki) were determined to be 2144 µmol/L for fast acetylators and 712 µmol/L for slow acetylators, using sulfamethazine as a test substrate.
• In Vivo Study: The effect of acetaminophen on NAT2 activity was further evaluated in 20 healthy volunteers. Participants were administered 1000 mg of acetaminophen every 6 hours for one day. NAT2 activity was measured using a urinary caffeine assay, which showed a significant reduction in NAT2 activity for both fast and slow acetylators after acetaminophen administration.
• Conclusion: The findings suggest that acetaminophen can inhibit NAT2 activity, which has implications for drug interactions and the metabolism of NAT2 substrates. This inhibition could lead to altered pharmacokinetics and potential side effects in individuals taking medications that are metabolized by NAT2.

摘要： 本研究调查了对乙酰氨基酚对肝脏N-乙酰转移酶2（NAT2）的抑制作用，该酶负责多种药物和外来物的乙酰化。研究包括体外和体内实验：

• 体外研究：在使用磺胺美唑作为测试底物的情况下，发现对乙酰氨基酚对人肝匀浆中的NAT2活性具有竞争性抑制作用。抑制常数（Ki）分别为2144 µmol/L（快速乙酰化者）和712 µmol/L（慢速乙酰化者）。
• 体内研究：进一步在20名健康志愿者中评估了对乙酰氨基酚对NAT2活性的影响。参与者每6小时服用1000 mg对乙酰氨基酚一天，使用尿液咖啡因检测评估NAT2活性，结果显示服用对乙酰氨基酚后，无论是快速还是慢速乙酰化者的NAT2活性都有显著下降。

结论：研究结果表明，对乙酰氨基酚可抑制NAT2活性，这对药物相互作用和NAT2底物的代谢具有重要意义。这种抑制可能导致药代动力学的改变和服用由NAT2代谢的药物的个体潜在的副作用。

对应化合物的CAS号

• 对乙酰氨基酚（Acetaminophen）: 103-90-2
• 磺胺美唑（Sulfamethazine）: 57-68-1