Nabumetone--a novel anti-inflammatory drug: bioavailability after different dosage regimens

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.