Journal of Radiation Industry (방사선산업학회지)

Korean Society of Radiation Industry (한국방사선산업학회)
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Non-clinical Trials using 14C-Acetaminophen to Validate Biomedical Accelerator Mass Spectrometry System

14C-아세트아미노펜 비임상시험을 통한 생체시료 분석용 가속질량분석기의 검증

  • Jinho Song (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Jae Hoon Shim (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Jung Bae Park (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Chang Su Yeo (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Soo Hyeon Bae (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Min Sun Choi (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Mi Hye Kwon (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Kyeong Min Kim (Korea Radio-Isotope Center for Pharmaceuticals, Korea Institute of Radiological and Medical Sciences)
  • 송진호 (한국원자력의학원 국가RI신약센터) ;
  • 심재훈 (한국원자력의학원 국가RI신약센터) ;
  • 박정배 (한국원자력의학원 국가RI신약센터) ;
  • 여창수 (한국원자력의학원 국가RI신약센터) ;
  • 배수현 (한국원자력의학원 국가RI신약센터) ;
  • 최민선 (한국원자력의학원 국가RI신약센터) ;
  • 권미혜 (한국원자력의학원 국가RI신약센터) ;
  • 김경민 (한국원자력의학원 국가RI신약센터)
  • Received : 2022.07.07
  • Accepted : 2023.06.12
  • Published : 2023.06.30
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Abstract

Pharmacokinetic (PK) data provide pivotal information in drug development, and they are usually first studied in the preclinical stage using various animals. However, quite often, animal PK data may not match with human PK, especially in metabolites. Thus, most regulatory agencies in the world make it mandatory to obtain metabolite information using 14C radiolabeled drug in human for small molecule drug candidates. However, such studies are expensive and time consuming and they are usually done at the end of Phase II trials using ~3.7 MBq of 14C labeled drug in a limited number of human subjects. Introduction of accelerator mass spectrometry (AMS) in this kind of study has revolutionized it. Since AMS can measure 14C level as close as natural abundance, it can quantify the amounts of 14C labeled drugs and their metabolites produced in human body that consumes less than the amount of 0.0037 MBq of 14C labeled drug, a very safe level of radioactive dose in human. Therefore, it is now possible to conduct human 14C studies safely in early clinical trials without spending hefty amount of money and time. Korea Radioisotope Center for Pharmaceuticals(KRICP) at Korea Institute of Biological and Medical Sciences(KIRAMS) has established an AMS facility in 2018, housing a 0.5MV AMS manufactured at the US National Electrostatics Corps (NEC). The AMS instrument has been validated using various standard samples that have been prepared at Lawrence Livermore National Laboratory in the US, a worldly reputable provider of AMS standards. In this paper, we present a mass balance study for acetaminophen in rats using AMS and prove that the study results are equivalent with those of literature, which shows the AMS facilities at KRICP has successfully installed and be ready to be used in the various PK studies using 14C labelled compounds for new drug development.

Keywords

Acknowledgement

본 논문은 2020년도 한국원자력의학원에서 발행한 방사성동위원소이용 신개념치료기술개발 플랫폼구축사업 최종보고서 데이터를 활용하여 재구성하였으며 과학기술정보통신부 한국원자력의학원 연구운영비지원사업(No.50539-2022)의 지원을 받아 수행되었음.

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