Title：Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man

标题：对乙酰氨基酚（扑热息痛）是人类中的一种选择性环氧化酶-2抑制剂

Authors: Hinz B, Cheremina O, Brune K

作者： Hinz B, Cheremina O, Brune K
Journal: FASEB Journal, 2008

期刊： FASEB Journal, 2008
Volume and Issue: 22(2), pages 383-390

卷号和期号： 第22卷，第2期，页码383-390
Publication Date: February 2008

出版日期： 2008年2月
PubMed ID: 17884974

Abstract：

For over three decades, acetaminophen (paracetamol) was believed to lack significant inhibition of peripheral prostanoids. Attempts to explain its action through inhibition of a central cyclooxygenase (COX)-3 have been dismissed. This study proposes that acetaminophen functions as a selective COX-2 inhibitor. The research involved assessing COX inhibition and pharmacokinetics in five volunteers who received a single 1000 mg dose of acetaminophen orally. Thromboxane B2 (COX-1) and prostaglandin E2 (COX-2) levels were measured in human whole blood both ex vivo and in vitro.

摘要：

在过去的三十多年里，扑热息痛（对乙酰氨基酚）被认为没有显著的抑制外周前列腺素的作用。通过抑制中枢环氧合酶（COX）-3来解释其作用的尝试已经被否定。这项研究提出，扑热息痛作为选择性COX-2抑制剂发挥作用。研究评估了五名志愿者在口服1000毫克扑热息痛后的COX抑制作用和药代动力学。通过体外和体内测量人类全血中的凝血诱导的血栓烷B2（COX-1）和脂多糖诱导的前列腺素E2（COX-2）。

Key findings include:

- Acetaminophen showed a 4.4-fold selectivity for COX-2 inhibition.

- After oral administration, COX-1 inhibition was 56% and COX-2 inhibition was 83%.

- Acetaminophen plasma levels remained above the in vitro IC50 for COX-2 for at least 5 hours post-administration.

- The study concludes that acetaminophen's analgesic and anti-inflammatory effects, along with its superior gastrointestinal safety profile compared to NSAIDs, can be attributed to its substantial COX-2 inhibition.

主要发现包括：

- 扑热息痛对COX-2抑制的选择性为4.4倍。

- 口服给药后，COX-1的抑制率为56%，COX-2的抑制率为83%。

- 扑热息痛血浆水平在给药后至少5小时内保持在COX-2的体外IC50以上。

- 研究得出结论，扑热息痛的镇痛和抗炎效果以及相对于NSAIDs的优越胃肠道安全性可归因于其显著的COX-2抑制作用。

Key Compounds and their CAS Numbers

Acetaminophen (Paracetamol): 103-90-2

Prostaglandin E2: 363-24-6