Maleev A, Vlahov V, Gruev I, Dierdorf D, Kostova N, Bacracheva N
Int J Clin Pharmacol Ther Toxicol. 1986 Aug;24(8):425-9.
The effectiveness of the nonsteroidal anti-inflammatory agent nabumetone is related to the formation of an active metabolite: 6-methoxy-2-naphthylacetic acid. The plasma concentrations of nabumetone and its active metabolite, after administration of 1,000 mg single dose p.o., are followed at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 30 and 48 h in 6 patients with laboratory evidence for functional liver insufficiency caused by liver cirrhosis, confirmed by biopsy. In the patients with liver insufficiency the mean values of Cmax and AUC0-24 h for 6-methoxy-2-naphthylacetic acid were 26.75 +/- 8.45 mg/l and 623.64 +/- 161.8 mg X h/l respectively. They did not differ significantly from the values observed in healthy volunteers [v. Schrader et al. 1983]. The Tmax-value was prolonged to 8 h, compared to 4 h Tmax-value of the volunteers. There is a tendency towards a reduced bioavailability of 6-methoxy-2-naphthylacetic acid after nabumetone administration in patients with a more severely expressed pathologic impairment, compared to patients with slight morphologic changes of the liver parenchyma.
非甾体抗炎药萘丁美酮的疗效与其活性代谢产物6-甲氧基-2-萘乙酸的形成有关。对6例经活检证实为肝硬化所致功能性肝功能不全的患者口服单剂量1000mg萘丁美酮后，在0、0.5、1、2、4、6、8、12、24、30和48小时监测萘丁美酮及其活性代谢产物的血浆浓度。肝功能不全患者中，6-甲氧基-2-萘乙酸的Cmax和AUC0-24 h平均值分别为26.75±8.45mg/L和623.64±161.8mg·h/L。这些值与健康志愿者中观察到的值[施拉德等人，1983年]无显著差异。与志愿者4小时的Tmax值相比，Tmax值延长至8小时。与肝实质形态学改变轻微的患者相比，在病理损害更严重的患者中，服用萘丁美酮后6-甲氧基-2-萘乙酸的生物利用度有降低的趋势。
