Archives of Pharmacal Research

  • 제28권11호
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  • Pages.1287-1292
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  • 2005
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

In Vitro Metabolism of a New Cardioprotective Agent, KR-33028 in the Human Liver Microsomes and Cryopreserved Human Hepatocytes

  • Kim Hyojin (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Yoon Yune-Jung (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Kim Hyunmi (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Cha Eun-Young (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Lee Hye Suk (Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University) ;
  • Kim Jeong-Han (School of Agricultural Biotechnology, Seoul National University) ;
  • Yi Kyu Yang (Bio-organic Science Division, Korea Research Institute of Chemical Technology) ;
  • Lee Sunkyung (Bio-organic Science Division, Korea Research Institute of Chemical Technology) ;
  • Cheon Hyae Gyeong (Bio-organic Science Division, Korea Research Institute of Chemical Technology) ;
  • Yoo Sung-Eun (Bio-organic Science Division, Korea Research Institute of Chemical Technology) ;
  • Lee Sang-Seop (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Shin Jae-Gook (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Liu Kwang-Hyeon (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
  • 발행 : 2005.11.01
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초록

KR-33028 (N-[4-cyano-benzo[b]thiophene-2-carbonyl]guanidine) is a new cardioprotective agent for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-33028 in human liver microsomes and to compare its metabolism with that of cryopreserved human hepatocytes. Human liver microsomal incubation of KR-33028 in the presence of NADPH and UDPGA resulted in the formation of four metabolites, M1, M2, M3, and M4. M1 and M2 were identified as 5-hydroxy-KR-33028 and 7-hydroxy-KR-33028, respectively, on the basis of LC/MS/MS analysis with the synthesized authentic standard. M3 and M4 were suggested to be dihydroxy-KR-33028 and hydroxy-KR-33028-glucuronide, respectively. Metabolism of KR-33028 in cryopreserved human hepatocytes resulted in the formation of M1, M2, and M4. These data show a good correlation between major metabolites formed in human liver microsomes and cryopreserved human hepatocytes. In addition, KR­33028 was found to inhibit moderately the metabolism of CYP1A2 substrates. Based on the results obtained metabolic pathway of KR-33028 is proposed.

키워드

참고문헌

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