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Quantifying exploratory low dose compounds in humans with AMS.使用 AMS 定量分析人体中的探索性低剂量化合物。
Adv Drug Deliv Rev. 2011 Jun 19;63(7):518-31. doi: 10.1016/j.addr.2010.10.009. Epub 2010 Oct 31.
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Practical experience of using human microdosing with AMS analysis to obtain early human drug metabolism and PK data.利用人类微剂量给药结合AMS分析获取早期人体药物代谢和药代动力学数据的实践经验。
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Addressing metabolite safety during first-in-man studies using ¹⁴C-labeled drug and accelerator mass spectrometry.在首次人体研究中使用¹⁴C标记药物和加速器质谱法评估代谢物安全性。
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Attomole detection of 3H in biological samples using accelerator mass spectrometry: application in low-dose, dual-isotope tracer studies in conjunction with 14C accelerator mass spectrometry.使用加速器质谱法对生物样品中的3H进行阿托摩尔检测:在与14C加速器质谱法结合的低剂量双同位素示踪研究中的应用。
Chem Res Toxicol. 1998 Oct;11(10):1217-22. doi: 10.1021/tx9801458.
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Human in Vivo Pharmacokinetics of [(14)C]Dibenzo[def,p]chrysene by Accelerator Mass Spectrometry Following Oral Microdosing.口服微剂量给药后,通过加速器质谱法测定[(14)C]二苯并[def,p] Chrysene的人体体内药代动力学。
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Simultaneous oral therapeutic and intravenous ¹⁴C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin.同时进行口服治疗和静脉¹⁴C-微剂量以确定沙格列汀和达格列净的绝对口服生物利用度。
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本文引用的文献

1
Early human ADME using microdoses and microtracers: bioanalytical considerations.使用微剂量和微示踪剂的早期人体药物代谢动力学、药物代谢和排泄:生物分析考量
Bioanalysis. 2010 Mar;2(3):441-54. doi: 10.4155/bio.10.8.
2
Practical experience of using human microdosing with AMS analysis to obtain early human drug metabolism and PK data.利用人类微剂量给药结合AMS分析获取早期人体药物代谢和药代动力学数据的实践经验。
Bioanalysis. 2010 Mar;2(3):429-40. doi: 10.4155/bio.10.6.
3
Human microdosing for the prediction of patient response.用于预测患者反应的人体微剂量给药。
Bioanalysis. 2010 Mar;2(3):373-6. doi: 10.4155/bio.10.3.
4
Microdosing: a valuable tool for accelerating drug development and the role of bioanalytical methods in meeting the challenge.微剂量给药:加速药物研发的宝贵工具以及生物分析方法在应对挑战中的作用
Bioanalysis. 2009 Oct;1(7):1293-305. doi: 10.4155/bio.09.107.
5
Accelerator mass spectrometry can be used to assess vitamin A metabolism quantitatively in boys in a community setting.加速器质谱法可用于在社区环境中定量评估男孩的维生素 A 代谢情况。
J Nutr. 2010 Sep;140(9):1588-94. doi: 10.3945/jn.110.125500. Epub 2010 Jul 21.
6
Significant human beta-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating.体内胸苷类似物掺入和放射性碳定年表明,人类β细胞的大量更替仅限于生命的头三十年。
J Clin Endocrinol Metab. 2010 Oct;95(10):E234-9. doi: 10.1210/jc.2010-0932. Epub 2010 Jul 21.
7
Accelerator mass spectrometry-enabled studies: current status and future prospects.基于加速器质谱的研究:现状与未来展望。
Bioanalysis. 2010 Mar;2(3):519-41. doi: 10.4155/bio.09.188.
8
Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability.非索非那定的药代动力学:微剂量评估和绝对口服生物利用度评估。
Eur J Pharm Sci. 2010 May 12;40(2):125-31. doi: 10.1016/j.ejps.2010.03.009. Epub 2010 Mar 20.
9
Recent advances in biomedical applications of accelerator mass spectrometry.加速器质谱技术在生物医学应用中的最新进展。
J Biomed Sci. 2009 Jun 17;16(1):54. doi: 10.1186/1423-0127-16-54.
10
Quantitation of NAD+ biosynthesis from the salvage pathway in Saccharomyces cerevisiae.酿酒酵母中补救途径中NAD+生物合成的定量分析。
Yeast. 2009 Jul;26(7):363-9. doi: 10.1002/yea.1671.

使用 AMS 定量分析人体中的探索性低剂量化合物。

Quantifying exploratory low dose compounds in humans with AMS.

机构信息

Vitalea Science, Inc, Davis, CA 95618, USA.

出版信息

Adv Drug Deliv Rev. 2011 Jun 19;63(7):518-31. doi: 10.1016/j.addr.2010.10.009. Epub 2010 Oct 31.

DOI:10.1016/j.addr.2010.10.009
PMID:21047543
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3062634/
Abstract

Accelerator Mass Spectrometry is an established technology whose essentiality extends beyond simply a better detector for radiolabeled molecules. Attomole sensitivity reduces radioisotope exposures in clinical subjects to the point that no population need be excluded from clinical study. Insights in human physiochemistry are enabled by the quantitative recovery of simplified AMS processes that provide biological concentrations of all labeled metabolites and total compound related material at non-saturating levels. In this paper, we review some of the exploratory applications of AMS (14)C in toxicological, nutritional, and pharmacological research. This body of research addresses the human physiochemistry of important compounds in their own right, but also serves as examples of the analytical methods and clinical practices that are available for studying low dose physiochemistry of candidate therapeutic compounds, helping to broaden the knowledge base of AMS application in pharmaceutical research.

摘要

加速器质谱分析是一项成熟的技术,其重要性不仅在于它是放射性标记分子的更好探测器。阿特摩尔灵敏度将临床研究对象中的放射性同位素暴露降低到无需排除任何人群参与临床研究的程度。通过定量回收简化的 AMS 过程,实现了人类生理化学的深入了解,该过程以非饱和水平提供所有标记代谢物和总相关化合物材料的生物浓度。在本文中,我们回顾了 AMS(14)C 在毒理学、营养学和药理学研究中的一些探索性应用。这些研究本身涉及到重要化合物的人体生理学化学,但也为研究候选治疗化合物低剂量生理学化学的分析方法和临床实践提供了范例,有助于拓宽 AMS 在药物研究中的应用知识库。