谷丙转氨酶和总胆红素浓度预测CYP3A的活性

Alanine Transaminase and Total Bilirubin Concentrations Predict CYP3A Activity

关键词:  微粒体酶CYP3A  肝功能测试  咪唑安定

Key words:  cytochrome P-450 CYP3A  liver function test  midazolam

摘要:

目的 探索肝功能指标是否可以预测不同肝功能患者的肝微粒体酶(CYP3A)的活性。方法 选择全身麻醉下手术患者45例，分成3组：正常肝功能组(正常组)，肝功能中度损伤组(中度损伤组)和终末期肝病组(终末期组)。每位患者静脉注射5 mg咪唑安定，2 h后采集静脉血检测咪唑安定(MDZ)以及主要代谢产物1’-羟基-咪唑安定(1’-OH-MDZ)的血浆药物浓度，以1’-OH-MDZ与MDZ计算CYP3A的活性。将肝功能指标参数与CYP3A活性进行多项回归。结果 正常组和中度损伤组的CYP3A活性差异没有显著性(P=0.332)，而终末期组的酶活性比正常组和中度损伤组低，差异具有统计学意义(P=0.000)。多项线性回归的结果显示CYP3A活性与血清谷丙转氨酶(ALT)浓度(R²=0.682，P=0.000)和总胆红素(TB)浓度(R²=0.519，P=0.002)具有线性关系。而其他因素如白蛋白(P=0.881)和碱性磷酸酶(P=0.497)与CYP3A活性没有线性关系。结论 终末期肝病患者CYP3A活性降低，血清ALT和TB浓度可以预测CYP3A的活性，因此肝功能检测ALT或者TB升高可以提示临床医生需要调整药物剂量。

Abstract:

OBJECTIVE To investigate the activity of CYP3A in patients with different liver function and whether serum concentrations of liver function indices may predict the CYP3A activity. METHODS Forty-five patients undergoing operation under general anesthesia were enrolled in the study, including 15 cases with normal liver function (normal group), 15 cases with moderate fatty liver according to both the results of ultrasonic diagnosis of moderate fatty liver and the laboratory results of elevated alanine transaminase less than 3 times the normal (moderate injury group), and 15 cases with end-stage liver disease (end stage group). Each patient received single dose of 5 mg midazolam intravenously. CYP3A activity was measured by plasma 1’hydroxymidsazolam/midazolam (1’-OH-MDZ/MDZ) ratio at 2 h after administration of midazolam. The correlations between function indices and CYP3A activity were evaluated by multiple linear regression RESULTS There was no significant difference of CYP3A activity between the patients in normal group and moderate injury group (P=0.332). The activity of CYP3A in end stage group was lower than in normal group and moderate injury group (P=0.000). Multiple linear regression analysis showed a statistically significant linear relationship between the activity of CYP3A and alanine transaminase (ALT, R²=0.682, P=0.000), and total bilirubin (TB, R²=0.519, P=0.002). There were no other factors, including albumin (ALB, P=0.881) and alkaline phosphatase (ALP, P=0.497), correlated with the activity of CYP3A. CONCLUSION The activity of CYP3A in patients with end-stage liver disease decreased. Serum concentrations of ALT and TB have a predictive value for CYP3A in patient with liver dysfuntion.