在红细胞中测量甲状腺酸聚氨酸的数量和在克罗恩病患者的应用
Hakmin Kim1,2, Kyeong-Seog Kim1,2, Sihyun Kim3,4
1Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.
Translational and clinical pharmacology
|July 14, 2025
概括
在红细胞中量化细胞内甲基酸多聚氨酸 (MTX-PGs) 对于监测克罗恩病治疗至关重要. 一种新的高灵敏度方法精确测量MTX-PGs,显示血水平不反映细胞内药物积累.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
- 临床化学 临床化学
背景情况:
- 甲托雷克萨特 (MTX) 是一种用于克罗恩氏病 (CD) 的叶酸对抗剂.
- 它的抗炎作用取决于细胞内转化为MTX多重胺酸 (MTX-PGs).
- 目前的血监测并不能准确地反映MTX的疗效,因为细胞内积累.
研究的目的:
- 建立一种高灵敏度的方法来量化CD患者的细胞内MTX-PGs.
- 评估血MTX水平与细胞内MTX-PGs之间的相关性.
主要方法:
- 开发了一种使用高酸脱蛋白化和HPLC-MS/MS的方法.
- 从CD患者的红细胞 (RBC) 中量化了三种MTX-PG.
- 验证了该方法的线性,精度和准确性.
主要成果:
- 对于MTX-PGs,已达到1 ng/mL的下限量化值.
- 证明了出色的线性 (1-400 ng/mL) 和令人满意的精度和准确性.
- 没有发现血MTX水平和RBCMTX-PGs之间的显著相关性 (p>0.5).
结论:
- 血MTX水平是细胞内MTX积累和CD治疗疗效的不可靠指标.
- 开发的定量方法是了解MTX代谢的宝贵工具.
- 这种方法可以促进改善治疗药物监测在CD的MTX治疗.
相关概念视频
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
272
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
272
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
237
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
237
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
204
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
204


