DRUG-METABOLISM IN LIVER-DISEASE - ACTIVITY OF HEPATIC MICROSOMAL METABOLIZING ENZYMES
DRUG-METABOLISM IN LIVER-DISEASE - ACTIVITY OF HEPATIC MICROSOMAL METABOLIZING ENZYMES
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DOI：
10.1002/cpt1979264483
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发表时间：
1979-01-01
影响因子：
6.7
通讯作者：
POWELL, LW
中科院分区：
文献类型：
--
作者：
FARRELL, GC;COOKSLEY, WGE;POWELL, LW
细胞色素P-450的浓度和微粒体酶芳烃羟化酶和乙基吗啡脱甲基酶的活性进行了测定，在肝组织活检从69例患者。同时测量安替比林半衰期（AP t1/2）作为药物代谢的体内标志物。药物代谢系统的每个指标的值变化很大，但轻度肝炎或非活动性肝硬化患者组的平均值与对照组无显著差异。重型肝炎或活动性肝硬化患者肝细胞色素P-450含量和芳烃羟化酶活性低于对照组，但乙基吗啡脱甲基酶活性在患者中无变化。除严重肝病患者外，所有患者的药物摄入均与药物代谢酶的增强相关;乙基吗啡脱甲基酶活性的增强比例大于芳烃羟化酶活性或细胞色素P-450浓度。芳烃羟化酶和乙基吗啡脱甲基酶的活动受到不同程度的肝脏疾病和药物摄入的影响，这一观察表明，在man. Correlations之间的t 1/2和肝脏药物氧化酶的肝微粒体药物代谢系统的功能异质性是弱的，即使当津贴在肝脏大小的变化。通过测量AP t1/2评估的体内药物代谢速率似乎与某些肝脏药物代谢酶的活性不密切相关。
The concentration of cytochrome P-450 and activities of the microsomal enzymes aryl hydrocarbon hydroxylase and ethylmorphine demethylase were measured in hepatic tissue obtained at biopsy from 69 patients. Antipyrine half-life (AP t1/2) was measured simultaneously as an in vivo marker of drug metabolism. Values for each index of the drug-metabolizing system varied greatly, but the mean values in groups of patients with mild hepatitis or inactive cirrhosis did not differ significantly from those of controls. Hepatic cytochrome P-450 content and aryl hydrocarbon hydroxylase activity were lower in patients with severe hepatitis or active cirrhosis than in controls, but ethylmorphine demethylase activity was unchanged in the patients. Drug ingestion was associated with enhancement of drug-metabolizing enzymes in all patients but those with severe liver disease; ethylmorphine demethylase activity was enhanced proportionately more than aryl hydrocarbon hydroxylase activity or cytochrome P-450 concentration. The observation that aryl hydrocarbon hydroxylase and ethylmorphine demethylase activities are influenced to a different extent by liver disease and by drug ingestion indicates functional heterogeneity of the hepatic microsomal drug-metabolizing system in man. Correlations between t 1/2 and hepatic drug oxidases were weak, even when allowance was made for variation in liver size. The rate of drug metabolism in vivo assessed by measuring AP t1/2 does not appear to be closely related to the activity of some hepatic drug-metabolizing enzymes.