Qu Z Q, Li X D, Liu H L, He P, Zhang X, Wu M C
Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Int J Clin Pharmacol Ther. 2007 Jan;45(1):55-62. doi: 10.5414/cpp45055.
CYP450 1A2 is constitutively expressed in liver. Phenacetin O-de-ethylation is a marker reaction for CYP450 1A2 activity. In this paper, the metabolism of phenacetin has been studied in patients with chronic hepatitis B or cirrhosis secondary to a hepatitis B virus infection. The possibility of using the phenacetin test in the evaluation of liver function in these subjects has also been tested.
Phenacetin pharmacokinetics and the recovery of its urinary metabolites were studied in 8 normal subjects, 16 patients with chronic hepatitis B and 12 patients with cirrhosis. The phenacetin test was performed in 18 normal subjects and 52 hepatocellular carcinoma (HCC) patients. The test was repeated in HCC patients after treatment with transcatheter arterial chemoembolization (TACE).
Compared with normal controls, phenacetin apparent clearance decreased by 47.0% (p < 0.05) and 78.7% (p < 0.01) in patients with chronic hepatitis B and cirrhosis, respectively. The recovery of phenacetin O-de-ethylated metabolites decreased by 24.6 and 72.4% (p < 0.01). 46 of 52 HCC patients (88.4%) had an abnormal phenacetin test before TACE, where the ratio of plasma total acetaminophen to phenacetin was below the lower limit of the normal control range. The ratio was less than 50% of normal controls in 6 HCC patients who had a deterioration in liver function from Child-Pugh class A to Child-Pugh class B after TACE.
The metabolism of phenacetin is impaired in patients with chronic hepatitis B and cirrhosis. The phenacetin test can predict the susceptibility of liver function to TACE in HCC patients.
细胞色素P450 1A2（CYP450 1A2）在肝脏中组成性表达。非那西丁O - 脱乙基化是CYP450 1A2活性的标志物反应。本文研究了慢性乙型肝炎或乙型肝炎病毒感染继发肝硬化患者中非那西丁的代谢情况。还测试了在这些受试者中使用非那西丁试验评估肝功能的可能性。
研究了8名正常受试者、16名慢性乙型肝炎患者和12名肝硬化患者的非那西丁药代动力学及其尿代谢产物的回收率。对18名正常受试者和52名肝细胞癌（HCC）患者进行了非那西丁试验。在经动脉化疗栓塞术（TACE）治疗后的HCC患者中重复进行该试验。
与正常对照组相比，慢性乙型肝炎患者和肝硬化患者中非那西丁的表观清除率分别降低了47.0%（p < 0.05）和78.7%（p < 0.01）。非那西丁O - 脱乙基代谢产物的回收率分别降低了24.6%和72.4%（p < 0.01）。52名HCC患者中有46名（88.4%）在TACE治疗前非那西丁试验异常，其中血浆对乙酰氨基酚与非那西丁的比值低于正常对照范围的下限。在6名TACE治疗后肝功能从Child - Pugh A级恶化为Child - Pugh B级的HCC患者中，该比值低于正常对照的50%。
慢性乙型肝炎和肝硬化患者中非那西丁的代谢受损。非那西丁试验可预测HCC患者肝功能对TACE的易感性。
