Drug Metabolizing Activity in Chronic Liver Disease: A Study Using Ultrasonically-Guided Needle Biopsy

Y. Kitao
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Abstract

Drug metabolizing activity in chronic liver disease was examined. In 53 patients with chronic liver disease, 7-methoxycoumarin (7-MC) 0-demethylase and 7-ethoxycoumarin (7-EC) 0-deethylase activities in liver specimens obtained by ultrasonically-guided liver biopsy were measured and compared with the elimination half-life (T1/2) of theophylline and biochemical liver function tests. Both the 0-dealkylase activities toward 7-MC and 7-EC in the liver were gradually decreased with progressive histological impairment of the liver to 32. 8% and 39. 6% of the control level, respectively, in patients with liver cirrhosis. Both the 0-dealkylase activities toward 7-MC and 7-EC in the liver inversely and exponentially correlated with the T1/2 of theophylline. These two 0-dealkylase activities correlated well with serum albumin content (Alb) , cholinesterase (ChE) , prothrombin time (PT), hepaplastintest (HPT) , cholesterol ester ratio (E/T) , zinc sulfate turbidity test (ZTT) , the ratio of branched chain amino acids to aromatic amino acids (BCAA/AAA) or indocyanine green test (ICG) , but not with GPT, LAP or total cholesterol. These findings indicate that the activity of drug metabolizing enzymes reflect hepatic functional capacity, and the measurement of these activities in specimens obtained by liver biopsy is useful for the clinical estimation of liver functions.
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慢性肝病药物代谢活性:超声引导下穿刺活检的研究
研究慢性肝病患者的药物代谢活性。对53例慢性肝病患者,采用超声引导下肝活检取肝标本,测定7-甲氧基香豆素(7-MC) 0-去甲基化酶和7-乙氧基香豆素(7-EC) 0-去乙基化酶活性,并与茶碱消除半衰期(T1/2)和肝功能生化指标进行比较。随着肝脏组织学损伤的进展,肝脏中0-脱烷基酶对7-MC和7-EC的活性逐渐降低至32。8%和39%。肝硬化患者分别为对照水平的6%。肝脏对7-MC和7-EC的脱烷基酶活性与茶碱的T1/2呈指数负相关。这两种0-脱烷基酶活性与血清白蛋白含量(Alb)、胆碱酯酶(ChE)、凝血酶原时间(PT)、肝磷脂酶(HPT)、胆固醇酯比(E/T)、硫酸锌浊度试验(ZTT)、支链氨基酸与芳香氨基酸之比(BCAA/AAA)、吲哚菁绿试验(ICG)相关性较好,与GPT、LAP和总胆固醇相关性不显著。这些结果表明,药物代谢酶的活性反映了肝功能容量,并且在肝活检获得的标本中测量这些活性对临床肝功能的估计是有用的。
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