[Bioavailability and tolerance of xanthinol nicotinate depot preparations. Comparison of a conventional 500 mg xanthinol nicotinate depot tablet with new 500 mg and 1 g depot tablets]. / Bioverfügbarkeit und Verträglichkeit verschiedener Xantinolnicotinat-Retardformen. Vergleich einer herkömmlichen 500-mg-Xantinolnicotinant-Retardtablette mit neuen 500-mg-und 1-g-Retardtabletten.

Bioavailability (therapeutic blood levels) and tolerance of two 500-mg xanthinol nicotinate retard tablet forms and one 1-g xanthinol nicotinate retard tablet (Complamin special) were tested in 11 (12) healthy volunteers. Despite the fact that both 500-mg retard tablets had different in vitro release rates the blood levels in man were similar. These results suggest that in vitro release rates of tablets do not predict corresponding blood levels in man. The tablet with a lower release rate also showed a distinctly lower flush rate. In respect to bioavailability and tolerance the 1-g xanthinol nicotinate retard tablet was comparable with corresponding dosages of 500-mg retard tablets. The dosage given was 2 X 500 mg or 1 g xanthinol nicotinate t.i.d. over a period of 10 days each.

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.

Nabumetone--a novel anti-inflammatory drug: the influence of food, milk, antacids, and analgesics on bioavailability of single oral doses.

The absorption and bioavailability of nabumetone, a novel anti-inflammatory drug, were investigated following administration of single oral doses alone, and with food, milk, antacids, and analgesics to healthy volunteers. Since no unchanged nabumetone has been found in human plasma [Mangan et al. unpublished information], the plasma level of the metabolite 6-methoxy-2-naphthylacetic acid was investigated. After doses of 250, 500, and 1000 mg nabumetone, maximum plasma concentrations of the major metabolite, 6-methoxy-2-naphthylacetic acid, were 9.76, 24.19, and 36.59 micrograms/ml, in nonfasting subjects. The 0-24 h and the 0-72 h areas under the plasma level curves together with the maximum plasma concentration reached, correlated strongly with the dosage level used. When nabumetone was given with food, the areas under the plasma level curve during the first 24 h and the maximum plasma concentrations were found to be significantly increased. No clinically relevant differences of plasma levels were seen when nabumetone was given to male and female subjects. The area under the plasma concentration curve and maximum plasma levels were significantly increased when the drug was given with milk compared to application with water or aluminum hydroxide. No significant differences could be found when the administration of nabumetone with aluminum hydroxide was compared with the administration with water. Co-administration of nabumetone with common analgesics, e.g., acetylsalicylic acid or paracetamol, did not significantly affect the plasma levels or the AUC values of 6-methoxy-2-naphthylacetic acid. The tolerance of nabumetone was found to be excellent in both fasting and nonfasting subjects. No adverse effects could be seen in hematology and clinical chemistry.