| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Yuki Showa University, School of Medicine, Department of Pharmacology, Research associate, 医学部, 助手 (40276572)
YASUHARA Hajime Showa University, School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (70053999)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Reliability of human surgical liver sample from hepatocellular carcinoma (HCC) patients and metasatic hepatic cancer (MHC) patients on the study of drug metabolism has been evaluated. Liver samples were donated from 7 HCC and 4 MHC patients. Liver sample was divided into three parts, carcinoma, peripheral parts (within 10 mm from carcinoma) and normal parts (10 mm or more further from carcinoma). Microsomal fraction in each parts, carcinoma, peripheral parts and normal parts, were prepared by conventional method. Human pooled hepatic microsome from Caucasian brain death patients was employed as a reference enzyme source. Microsomal Cytochrome P450 (CYP) enzyme activity, CYP1A2 (Caffeine, Ethoxyresorfin), 2C9 (Warfarin), 2C19 (Mephenytoin), 2D6 (Bufuralol), 2E1 (Chlorzoxazone) and 3A4 (Midazolam, Testosterone), were analyzed by using typical substrates. HPLC method was employed for the determination of each enzyme activity. CYP enzymes activity in normal parts was variated from 2 to 5 fold. Difference of CYP activity between normal parts and peripheral parts were within 2 fold in all liver samples. Furthermore, mean activity in 7 liver samples in each CYP enzymes and pooled microsome were quite similar in most of CYP enzymes. In CYP2C19, however, enzyme activity was quite low compared with pooled microsome. In conclusion, human surgical liver samples will be one of the enzyme sources for the estimation of drug metabolism in human. Further study will be needed on the lower activity on CYP 2C19 from surgical liver samples.
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