• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

白蛋白融合生长激素 TV-1106 对人肝细胞 CYP 酶表达的直接和细胞因子介导的影响。

Direct and cytokine-mediated effects of albumin-fused growth hormone, TV-1106, on CYP enzyme expression in human hepatocytes in vitro.

机构信息

Sekisui XenoTech, LLC Kansas City KS USA.

Teva Pharmaceutical Industries Ltd Petach Tikva Israel.

出版信息

Pharmacol Res Perspect. 2018 Apr 16;6(3):e00397. doi: 10.1002/prp2.397. eCollection 2018 Jun.

DOI:10.1002/prp2.397
PMID:29721322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5911691/
Abstract

Some biologics can modulate cytokines that may lead to changes in expression of drug-metabolizing enzymes and cause drug-drug interactions (DDI). DDI potential of TV-1106-an albumin-fused growth hormone (GH)-was investigated. In this study, human blood was exposed to recombinant human growth hormone (rhGH) or TV-1106, followed by isolation of the plasma and its application to human hepatocytes. While the treatment of blood with rhGH increased multiple cytokines, treatment of blood with TV-1106 had no effect on any of the nine cytokines tested. The interleukin (IL)-6 concentration was higher in the rhGH then in the TV-1106-treated plasma (<.05). While rhGH had little or no effect on CYP1A2 or CYP2C19 mRNA but increased CYP3A4 mRNA twofold, TV-1106 had little or no effect on cytochrome P450 (CYP) mRNAs in hepatocytes. Although the plasma from rhGH-treated blood lowered CYP1A2 activity, the TV-1106 plasma had no effect on CYP activities. The CYP1A2 activity was lower in the rhGH- then in the TV-1106-plasma treated hepatocytes (<.05). The results indicated that fusing GH with albumin made TV-1106 an unlikely participant of CYP1A2, CYP2C19 or CYP3A4-facilitated, direct or cytokine-driven DDI.

摘要

有些生物制剂可以调节细胞因子，从而导致药物代谢酶的表达发生变化，并引起药物相互作用（DDI）。研究了 TV-1106（一种与白蛋白融合的生长激素（GH））的 DDI 潜力。在这项研究中，用人重组生长激素（rhGH）或 TV-1106 处理人血液，然后分离血浆并将其应用于人肝细胞。rhGH 处理血液会增加多种细胞因子，而 TV-1106 处理血液对测试的 9 种细胞因子均无影响。rhGH 处理后的血浆中白细胞介素（IL）-6 浓度高于 TV-1106 处理后的血浆（<0.05）。rhGH 对 CYP1A2 或 CYP2C19 mRNA 几乎没有影响，但使 CYP3A4 mRNA 增加两倍，而 TV-1106 对肝细胞中的细胞色素 P450（CYP）mRNA 几乎没有影响。虽然 rhGH 处理后的血液血浆降低了 CYP1A2 活性，但 TV-1106 血浆对 CYP 活性没有影响。rhGH 处理后的血浆中 CYP1A2 活性低于 TV-1106 处理后的血浆（<0.05）。结果表明，将 GH 与白蛋白融合使 TV-1106 不太可能参与 CYP1A2、CYP2C19 或 CYP3A4 介导的直接或细胞因子驱动的 DDI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/661c/5911691/3a12d3ae07a5/PRP2-6-e00397-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/661c/5911691/28b4de6b08d8/PRP2-6-e00397-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/661c/5911691/3a12d3ae07a5/PRP2-6-e00397-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/661c/5911691/28b4de6b08d8/PRP2-6-e00397-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/661c/5911691/3a12d3ae07a5/PRP2-6-e00397-g002.jpg

相似文献

1
Direct and cytokine-mediated effects of albumin-fused growth hormone, TV-1106, on CYP enzyme expression in human hepatocytes in vitro.白蛋白融合生长激素 TV-1106 对人肝细胞 CYP 酶表达的直接和细胞因子介导的影响。
Pharmacol Res Perspect. 2018 Apr 16;6(3):e00397. doi: 10.1002/prp2.397. eCollection 2018 Jun.
2
Cryopreserved human hepatocytes as alternative in vitro model for cytochrome p450 induction studies.冷冻保存的人肝细胞作为细胞色素P450诱导研究的替代体外模型。
In Vitro Cell Dev Biol Anim. 2003 Jul-Aug;39(7):283-7. doi: 10.1290/1543-706X(2003)039<0283:CHHAAI>2.0.CO;2.
3
Anti-CD28 monoclonal antibody-stimulated cytokines released from blood suppress CYP1A2, CYP2B6, and CYP3A4 in human hepatocytes in vitro.抗CD28单克隆抗体刺激血液释放的细胞因子在体外可抑制人肝细胞中的CYP1A2、CYP2B6和CYP3A4。
Drug Metab Dispos. 2015 Jan;43(1):42-52. doi: 10.1124/dmd.114.060186. Epub 2014 Oct 17.
4
De-risking bio-therapeutics for possible drug interactions using cryopreserved human hepatocytes.使用冷冻保存的人肝细胞降低生物治疗药物发生药物相互作用的风险。
Curr Drug Metab. 2012 Sep 1;13(7):923-9. doi: 10.2174/138920012802138589.
5
Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes.丁基羟基甲苯、姜黄素、没食子酸丙酯和噻苯达唑对培养的人肝细胞中细胞色素P450亚型的影响。
Xenobiotica. 2008 Jun;38(6):574-86. doi: 10.1080/00498250802008615.
6
Effects of interleukin-6 (IL-6) and an anti-IL-6 monoclonal antibody on drug-metabolizing enzymes in human hepatocyte culture.白细胞介素-6（IL-6）及其单克隆抗体对人肝细胞培养中药物代谢酶的影响。
Drug Metab Dispos. 2011 Aug;39(8):1415-22. doi: 10.1124/dmd.111.038679. Epub 2011 May 9.
7
Comparison of inducibility of CYP1A and CYP3A mRNAs by prototypical inducers in primary cultures of human, cynomolgus monkey, and rat hepatocytes.在人、食蟹猴和大鼠肝细胞原代培养物中，典型诱导剂对CYP1A和CYP3A mRNA诱导能力的比较。
Drug Metab Pharmacokinet. 2007 Jun;22(3):178-86. doi: 10.2133/dmpk.22.178.
8
Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture.细胞因子对原代培养人肝细胞中CYP1A1、CYP1A2和CYP3A4诱导表达的差异作用。
Hepatology. 1995 Oct;22(4 Pt 1):1143-53.
9
Asenapine and iloperidone decrease the expression of major cytochrome P450 enzymes CYP1A2 and CYP3A4 in human hepatocytes. A significance for drug-drug interactions during combined therapy.阿塞那平与伊潘立酮可降低人肝细胞中主要细胞色素P450酶CYP1A2和CYP3A4的表达。这对联合治疗期间的药物相互作用具有重要意义。
Toxicol Appl Pharmacol. 2020 Nov 1;406:115239. doi: 10.1016/j.taap.2020.115239. Epub 2020 Sep 14.
10
Oncostatin M down-regulates basal and induced cytochromes P450 in human hepatocytes.
J Pharmacol Exp Ther. 1998 Apr;285(1):127-34.

本文引用的文献

1
Albumin and its application in drug delivery.白蛋白及其在药物递送中的应用。
Expert Opin Drug Deliv. 2015 May;12(5):793-812. doi: 10.1517/17425247.2015.993313. Epub 2014 Dec 18.
2
Anti-CD28 monoclonal antibody-stimulated cytokines released from blood suppress CYP1A2, CYP2B6, and CYP3A4 in human hepatocytes in vitro.抗CD28单克隆抗体刺激血液释放的细胞因子在体外可抑制人肝细胞中的CYP1A2、CYP2B6和CYP3A4。
Drug Metab Dispos. 2015 Jan;43(1):42-52. doi: 10.1124/dmd.114.060186. Epub 2014 Oct 17.
3
A reversible albumin-binding growth hormone derivative is well tolerated and possesses a potential once-weekly treatment profile.
一种可还原的白蛋白结合型生长激素衍生物具有良好的耐受性，并具有潜在的每周一次的治疗方案。
J Clin Endocrinol Metab. 2014 Oct;99(10):E1819-29. doi: 10.1210/jc.2014-1702. Epub 2014 Jul 11.
4
Critical review of preclinical approaches to investigate cytochrome p450-mediated therapeutic protein drug-drug interactions and recommendations for best practices: a white paper.临床前方法研究细胞色素 P450 介导的治疗性蛋白药物相互作用的评价及最佳实践建议：白皮书。
Drug Metab Dispos. 2013 Sep;41(9):1598-609. doi: 10.1124/dmd.113.052225. Epub 2013 Jun 21.
5
Randomized trial of albinterferon alfa-2b every 4 weeks for chronic hepatitis C virus genotype 2/3.随机试验研究慢性丙型肝炎病毒基因型 2/3 患者每 4 周接受一次 albinterferon alfa-2b 治疗的效果。
J Viral Hepat. 2012 Sep;19(9):623-34. doi: 10.1111/j.1365-2893.2012.01586.x. Epub 2012 Mar 21.
6
Long-term safety of recombinant human growth hormone in children.重组人生长激素治疗儿童的长期安全性。
J Clin Endocrinol Metab. 2010 Jan;95(1):167-77. doi: 10.1210/jc.2009-0178. Epub 2009 Nov 11.
7
In vitro inhibition and induction of human liver cytochrome p450 enzymes by milnacipran.米那普仑对人肝细胞色素 P450 酶的体外抑制和诱导作用。
Drug Metab Dispos. 2009 Oct;37(10):2045-54. doi: 10.1124/dmd.109.028274. Epub 2009 Jul 16.
8
Long-term safety of recombinant human growth hormone in turner syndrome.重组人生长激素在特纳综合征中的长期安全性。
J Clin Endocrinol Metab. 2008 Feb;93(2):344-51. doi: 10.1210/jc.2007-1723. Epub 2007 Nov 13.
9
Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes.炎症细胞因子对人肝细胞中细胞色素P450 2C、2B6和3A4 mRNA水平的基因特异性影响。
Drug Metab Dispos. 2007 Sep;35(9):1687-93. doi: 10.1124/dmd.107.015511. Epub 2007 Jun 18.
10
Sexually dimorphic regulation of hepatic isoforms of human cytochrome p450 by growth hormone.
J Pharmacol Exp Ther. 2006 Jan;316(1):87-94. doi: 10.1124/jpet.105.093773. Epub 2005 Sep 13.