非那西丁代谢试验与^(13)C-美沙西丁呼气试验在正常志愿者中的重复性和相关性

Reproducibility and correlation of phenacetin metabolism test and ^(13)C-methacetin breath test in healthy volunteers

目的比较13C-美沙西丁呼气试验与非那西丁代谢试验在正常志愿者中的重复性、相关性和性别差异。方法30例健康志愿者分别进行了2次非那西丁试验和2次13C-美沙西丁呼气试验,观察其重复性与相关性,以及年龄性别的影响。使用高效液相色谱法(HPLC)测定服药后2h血清非那西丁及其代谢产物总醋氨酚。13C-美沙西丁试验由红外线质谱仪测定40min最大浓度(Dosemax40),及40min和120min累积丰度(Cum40、120min)。结果非那西丁试验和13C-美沙西丁试验的重复试验显示了良好的重现性,但此两项试验的个体间差异和个体内差异均较大,其中非那西丁浓度(Phe)的差异最大,其范围为6.3%～137%,血清总醋氨酚(∑Ace)最小,为2.1%～39.5%。个体间差异也较大,其中Phe最大,为107.8%。Dose40最小,为27%。结论非那西丁代谢试验和13C-美沙西丁代谢试验有较好的重现性,但个体之间差异较大。二者在早期有较好的相关性。性别与年龄对二者均无影响。

Objective ^13C-methacetin breath test and phenacetin metabolism test are two promising tools for the assessment of liver function. ^13C-methacetin O-demethylation and phenacetin O-deethylation are mediated by cytochrome P450 1A2 （CYP1A2）. To determine the reproducibility and the correlation between the two tests. Methods 30 healthy volunteers underwent both phenacetin metabolism test and ^13C-methaeetin breath test twice to assess the reproducibility and correlation of these tests. For phenacetin metabolism test, the levels of plasma phenacetin （Phe）, plasma total- acetaminophen（ ∑Ace） were assayed by HPLC. The dose ratio of ^13CO2/12 CO2 at 20 （Dose20） or 40 minutes（Dose40） after ^13C-methacetin administration and the cumulative percentages of the administered dose of ^13CO2 recovered over 40 min （CUM40） and 120 min （CUM120） were calculated, respectively. Results There were no significant differences between the mean values of the main parameters of the two tests, but marked intra-individual and inter-individual variations for each parameter were noted, among which Phe had the largest inter- （6.3%- 137% ）and intra-individual variance （107. 8 %）. Dose20, Dose40, CUM40 and CUM120 were negatively correlated with plasma phenacetin levels whereas only Dose20 positively correlated were with total plasma levels of acetaminophen（r = 0. 418 ,P = 0.03）. Age and gender had no effect on the results of these two tests. Conclusion Phenacetin metabolism test and ^13C-methacetin breath test show good group hut poor individual reproducibility. These two tests have good correlations at early stage.