Terziivanov D, Maleev A, Vlahov V
Int J Clin Pharmacol Ther Toxicol. 1987 Apr;25(4):208-13.
The effect of presystemic elimination of nabumetone disposition was evaluated in 6 cirrhotic patients after oral administration of a single dose of 1000 mg of the drug. The data revealed the major role of hepatic metabolism in the removal of the drug from the body. The relatively high values of hepatic plasma excretion ratio (= 0.60 +/- 0.04) and of the total intrinsic clearance (= 90.74 +/- 15.87 l/h) places nabumetone between drugs with intermediate properties; clearance being partly dependent on plasma (blood) flow rate and on the hepatic metabolism whose systemic availability was 32% of the dose. Very good coincidence was obtained when ranging patients according to morphological evaluation of liver impairments was compared to the values of nabumetone disposition parameters. There was a statistically significant positive correlation (r = 0.831, p less than 0.05) between the fraction of the dose reaching the systemic circulation, f, and the gamma-GT "normalization index" (i.e., ratio between the observed decrease of serum gamma-glutamyl transpeptidase activity and the pretreatment difference from the upper normal value). A definite interpretation of the data cannot be provided until more knowledge about the effect of 6-mO-2-naphthylacetic acid on nabumetone metabolism is available.
在6例肝硬化患者口服单剂量1000 mg萘丁美酮后，评估了萘丁美酮处置的首过消除效应。数据显示肝脏代谢在药物从体内清除过程中起主要作用。肝血浆排泄率（= 0.60±0.04）和总内在清除率（= 90.74±15.87 l/h）的相对较高值使萘丁美酮介于具有中等性质的药物之间；清除率部分取决于血浆（血液）流速和肝脏代谢，其全身可用性为剂量的32%。根据肝脏损伤的形态学评估对患者进行分类，并与萘丁美酮处置参数值进行比较时，得到了很好的一致性。到达体循环的剂量分数f与γ-谷氨酰转肽酶“标准化指数”（即观察到的血清γ-谷氨酰转肽酶活性下降与预处理时与正常上限值的差异之比）之间存在统计学上显著的正相关（r = 0.831，p＜0.05）。在获得更多关于6 - mO - 2 - 萘乙酸对萘丁美酮代谢影响的知识之前，无法对数据进行明确解释。
