Nabumetone pharmacokinetics in patients with varying degrees of renal impairment.

The pharmacokinetics of 1 g of oral nabumetone were studied in 20 patients divided into three groups according to the creatinine clearance rate of each. Pharmacokinetic assessment was made on the presence of the major and active metabolite found in the plasma, 6-methoxy-2-naphthylacetic acid, BRL 10720. Although the differences in the kinetic parameters measured in the three groups of patients were not statistically significant, that the drug should be used with care in patients with impaired renal function until additional data are available.

Metabolism of nabumetone (BRL 14777) by various species including man.

Radiotracer methodology was used to study the metabolic fate of 4-(6-methoxy-2-naphthyl)-butan-2-one (nabumetone) after oral administration to rats, mice, rabbits, dogs, rhesus monkeys and healthy human subjects. Parent compound was not detected in plasma and urine and the major circulating metabolite in all species was identified as 6-methoxy-2-naphthylacetic acid, a compound known to possess anti-inflammatory activity. Metabolites were mainly excreted in urine from which four principal metabolites were isolated and identified by mass spectrometry and independent synthesis. Pathways involving O-demethylation, reduction of the ketone group and oxidation of the butanone side-chain to acetic acid occurred in all species, but the ratios of the metabolic end-products tended to be species dependent. In the rat about half of the administered nabumetone was oxidized to the pharmacologically active acid metabolite.

Bioavailability and pharmacokinetics of clavulanic acid in healthy subjects.

The bioavailability and pharmacokinetics of clavulanic acid were studied following oral solution and rapid intravenous administration to healthy volunteers. Plasma and urine samples were collected at frequent intervals following dose administration and were assayed for clavulanic acid by an enzyme inhibition method. Plasma data after intravenous administration were subjected to pharmacokinetic analysis using a two-compartment open model. The mean absolute bioavailability of clavulanic acid from oral solution was 0.75, derived from both urine and plasma data. No changes in the disposition pharmacokinetics of clavulanic acid with route were found, with a mean renal clearance of 0.1051 X min-1 and mean terminal elimination rate constant of 0.0134 min-1.

A pharmacokinetic study of the active metabolite of nabumetone in young healthy subjects and older arthritis patients.

We have performed a detailed pharmacokinetic study of the plasma concentrations of the major active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid (6 MNA), attained after a single dose and during chronic administration comparing the results of a group of young healthy volunteers with those of a group of elderly arthritic patients. The latter had higher peak plasma concentrations of 6 MNA and slower rates of elimination but there is no tendency for the drug to accumulate unpredictably in the old. Disease activity also influences plasma concentration, those with more active disease, and lower serum albumin concentrations had lower AUC values.