Department of Gastroenterology, Central Hospital of Xuhui District, Shanghai, China.
J Dig Dis. 2010 Dec;11(6):358-63. doi: 10.1111/j.1751-2980.2010.00463.x.
To evaluate human liver reserve function (LRF) by a simple and efficient method for measuring serum concentrations of phenacetin and its metabolites.
Overall 20 patients with liver cirrhosis (Child-Pugh score ≥ 7, aged 48-79 years), 30 healthy young volunteers (aged 18-40 years), and 20 healthy elderly volunteers (aged 61-80 years) were enrolled. All participants received a single oral dose of 0.5 g phenacetin. Liquid chromatography tandem mass spectrometry was used to determine the serum concentrations of phenacetin and its metabolites, including acetaminophen, acetaminophen glucuronide and acetaminophen sulfate.
The serum concentration of phenacetin was significantly higher in cirrhotic patients than those in either of the healthy volunteer groups (P < 0.001). It was higher in healthy elderly volunteers than that in healthy young ones but there was no statistically significant difference (P > 0.05) between them. The serum concentrations of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate were significantly lower in cirrhotic patients than in the healthy controls (P < 0.001). The serum concentrations of these three metabolites in healthy elderly volunteers were lower than those in healthy younger volunteers but again, there was no statistical significant difference (P > 0.05). The serum concentration of acetaminophen in healthy male volunteers was significantly higher than that in the women (P < 0.05).
Monitoring cytochrome P450 1A2 (CYP450 1A2)-mediated phenacetin metabolism is a simple and efficient method for evaluating human LRF. This method would warrant further validation in a large cohort clinical study.
通过一种简单有效的方法测量对乙酰氨基酚及其代谢物的血清浓度来评估人类肝储备功能（LRF）。
共纳入 20 例肝硬化患者（Child-Pugh 评分≥7，年龄 48-79 岁）、30 名健康年轻志愿者（年龄 18-40 岁）和 20 名健康老年志愿者（年龄 61-80 岁）。所有参与者均单次口服 0.5 g 对乙酰氨基酚。采用液相色谱-串联质谱法测定对乙酰氨基酚及其代谢物（包括对乙酰氨基酚、对乙酰氨基酚葡萄糖醛酸和对乙酰氨基酚硫酸盐）的血清浓度。
肝硬化患者的血清对乙酰氨基酚浓度明显高于健康志愿者组（P＜0.001），健康老年志愿者的血清对乙酰氨基酚浓度高于健康年轻志愿者，但差异无统计学意义（P＞0.05）。肝硬化患者的血清对乙酰氨基酚葡萄糖醛酸和对乙酰氨基酚硫酸盐浓度明显低于健康对照组（P＜0.001）。健康老年志愿者的这三种代谢物的血清浓度均低于健康年轻志愿者，但差异无统计学意义（P＞0.05）。健康男性志愿者的血清对乙酰氨基酚浓度明显高于女性志愿者（P＜0.05）。
监测细胞色素 P450 1A2（CYP450 1A2）介导的对乙酰氨基酚代谢是评估人类 LRF 的一种简单有效的方法。该方法需要在更大的队列临床研究中进一步验证。
