Liver insufficiency as a factor modifying the pharmacokinetic characteristic of the preparation nabumetone.
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.
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D002074:Butanones / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000077430:Nabumetone; D009280:Naphthaleneacetic Acids / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D009280:Naphthaleneacetic Acids; C044612:6-methoxy-2-naphthylacetic acid; D000077430:Nabumetone