von Schrader H W, Buscher G, Dierdorf D, Mügge H, Wolf D
Int J Clin Pharmacol Ther Toxicol. 1984 Dec;22(12):672-6.
The bioavailability of nabumetone after different multiple dosing regimens was investigated in healthy male volunteers by determining the main plasma metabolite 6-methoxy-2-naphthylacetic acid. The mean steady state morning plasma level was higher when 1000 mg nabumetone were administered, once daily, at night than after the application of 500 mg twice daily (in the morning and in the evening). There was only a small further increase of the mean steady state morning level when the dose was increased to 1000 mg b.d. In all application regimens the steady state was reached on day 3. The dosage of 1000 mg, once daily, at night with and without a loading dose of 1000 mg in the morning of the first day were compared. When a loading dose was administered the plasma levels rose very quickly to higher values but reached the same mean on day 3 as when given without the loading dose. The half-lives of the terminal beta-phase with mean values of 22.77 h and 22.0 h are of the same order of magnitude as those found in single dose studies. It can be concluded from these results that a dose regimen of 1000 mg once daily, at night would be preferable.
通过测定主要血浆代谢物6-甲氧基-2-萘乙酸，在健康男性志愿者中研究了不同多剂量给药方案后萘丁美酮的生物利用度。当每晚一次服用1000 mg萘丁美酮时，早晨的平均稳态血浆水平高于每日两次（早晨和晚上）服用500 mg后的水平。当剂量增加到每日两次1000 mg时，早晨的平均稳态水平仅略有进一步升高。在所有给药方案中，第3天达到稳态。比较了每晚一次服用1000 mg且第一天早晨有无1000 mg负荷剂量的情况。给予负荷剂量时，血浆水平迅速升至更高值，但第3天的平均值与未给予负荷剂量时相同。终末β相的半衰期平均值分别为22.77小时和22.0小时，与单剂量研究中发现的半衰期处于同一数量级。从这些结果可以得出结论，每晚一次服用1000 mg的给药方案更为可取。
