碳-14同位素標誌藥物於藥物安全性試驗之應用

Application of Radioisotope Carbon-14 Labeled Compounds to Study Drug Safety

陳威希(Wei-Hsi Chen) ； 張志賢(Chih-Hsien Chang)

《化學》 76卷4期 (2018/12) Pp. 329-336

https://doi.org/10.6623/chem.201812_76(4).001

摘要

化學物質在生命體內的互動歷程與作用機制必須充分掌握以保障用藥安全。研究新藥在體內吸收、分佈、代謝及排除速率、代謝物鑑定與定量、排除路徑等資料，是新藥大規模應用（臨床試驗三期）申請審查之前必須詳載。應用碳-14同位素具有輻射示蹤特性，於臨床前或臨床一、二期試驗，是國際新藥申請審查機構普遍認可的有效方法。然而碳-14半衰期長達5700年，輻射疑慮是應用此技術的障礙。本文簡介輻射同位素應用於研究生物活性分子體內分布的原理、比較各種同位素特性。文中討論碳-14標誌藥物動物試驗作業過程、檢體中碳-14藥物暨代謝物含量分析方法、碳-14輻射效應及實驗室管理等。核能研究所是國內輻射物質應用與研究的國家級研究機構，正著手建立應用碳-14藥物代謝分析技術平台，將能為新化學物質在生物體應用研發的產業界、學術研究及政府機構提供技術服務，協助政府振興國內生技新藥產業、增益國人健康福祉，將扮演槓桿效應支點的關鍵角色。

關鍵字

藥物代謝 ； 藥物動力學 ； 同位素標誌 ； 碳-14 ； 輻射示蹤

並列摘要

To assure drug safety, it is critical to clarify the history, interaction mechanisms as well as fate and transport of the xenobiotics in biosystems. Data related to the study of adsorption, distribution, metabolism, and excretion (ADME) of a new chemical entity (NCE) in vivo have to be disclosed clearly in new drug applications (NDAs) for phase III clinical trials. The application of traceable radioisotope carbon-14 labeled NCE in animal models to collect ADME data is gold standard, and it is accepted by NDA approval organizations all over the world. However, the half-life of carbon-14 is more than 5700 years, and the conscience that radioactivity lasts forever is an obstacle that must be overcome. Thus, the aim of this manuscript is to illustrate the myth surrounding the utilization of carbon-14 to evaluate the safety of NCEs in live animals. This review discusses the past use of radioisotopes to study the mechanisms and phenomena of substances in biosystems, as well as the character and protection criteria from radio-effects of carbon-14. The process of using carbon-14 labeled compounds to study ADME and pharmacokinetic (PK), analytical methods, and the meaning of data is also discussed. The Institute of Nuclear Energy Research (INER) is a national institution with expertise in radio-substance application and investigation. The technical platform for the manipulation of carbon-14 labeled compounds and the determination of its interactive behavior with biosystems is being established by the INER, and it will provide technical services to industries, fundamental sciences and government al agencies. The vision of the platform is to play a key role as the pivot of a leverage effect, to assist the government in their efforts to promote biotechnology industries in Taiwan, while improving the health of citizens.

並列關鍵字

Drug metabolism ； Pharmacokinetics ； Isotope label ； Carbon-14 ； Radio-traceable