von Mandach U, Jost G, Preisig R
Schweiz Med Wochenschr. 1985 May 11;115(19):651-8.
The metabolic activity of the hepatic cytochrome P450 system was studied in 53 ambulatory subjects. 18 of these were cirrhotics and 23 had non-cirrhotic liver disease, documented by biopsy, serologic, ultrasound or computerized tomography findings, and characterized by quantitative liver function tests, such as galactose elimination capacity and indocyanine green fractional clearance. For comparison, 12 normal control subjects were also included. All subjects were given 10 mg/kg body weight antipyrine and saliva concentrations determined with an HPLC-method at 24 and 48 hours after dosing. Antipyrine saliva clearance (ASC) was calculated according to a two-point method (Cl1), and compared with a one-point method (Cl2) using the 24 h sample only. These subjects also underwent an aminopyrine breath test (ABT), breath samples being collected at regular intervals during 60 minutes following injection of a tracer dose of 1.5 muCi (14C-dimethylamino)antipyrine. Cl1 and Cl2 correlated strongly (r = 0.93). On the basis of smaller variations (particularly in control subjects), better definition of disease severity and convenience and time saving, Cl2 is to be preferred. Comparison of Cl2 with ABT showed that both procedures apparently quantify overlapping enzymatic activities. However, the relationship between Cl2 and ABT values, albeit highly significant (r = 0.72), suggests that only about half of the variables are subject to the same determinant. In addition, a positive intercept of the regression line extrapolated to the Cl2 axis points to quantitatively important extrahepatic breakdown of antipyrine. The results suggest that, in view of the wide variation in normal values (presumably in part influenced by exogenous pollutants), ASC only provides an approximation of hepatic metabolic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
在53名非卧床受试者中研究了肝细胞色素P450系统的代谢活性。其中18名是肝硬化患者,23名患有非肝硬化性肝病,通过活检、血清学、超声或计算机断层扫描结果确诊,并通过定量肝功能试验进行特征描述,如半乳糖清除能力和吲哚菁绿分数清除率。作为对照,还纳入了12名正常受试者。所有受试者均给予10mg/kg体重的安替比林,并在给药后24小时和48小时用高效液相色谱法测定唾液浓度。根据两点法(Cl1)计算安替比林唾液清除率(ASC),并仅使用24小时样本与单点法(Cl2)进行比较。这些受试者还进行了氨基比林呼气试验(ABT),在注射1.5μCi(14C-二甲基氨基)安替比林示踪剂量后的60分钟内定期采集呼气样本。Cl1和Cl2相关性很强(r = 0.93)。基于较小的变异性(特别是在对照受试者中)、对疾病严重程度的更好界定以及便利性和节省时间,Cl2更受青睐。Cl2与ABT的比较表明,两种方法显然都在量化重叠的酶活性。然而,Cl2与ABT值之间的关系虽然高度显著(r = 0.72),但表明只有约一半的变量受相同因素决定。此外,外推到Cl2轴的回归线的正截距表明安替比林在肝外有重要的定量分解。结果表明,鉴于正常值差异很大(可能部分受外源性污染物影响),ASC仅提供了肝脏代谢活性的一个近似值。(摘要截短至250字)