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

Abstract

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 unpublished information], the plasma level of the metabolite 6-methoxy-2-naphthylacetic acid was investigated.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.