The effect of age on the plasma protein binding of pentobarbitone in the mouse. A brief note.

Old mice show an increased sensitivity to parenteral pentobarbitone compared with young adult mice, despite similar plasma concentrations of the drug. One factor may be an alteration in the binding of barbiturate to the plasma protein, perhaps consequent on reduced hepatic synthesis of plasma protein with advancing age. As part of a study of the effect of age upon the pharmacological and adaptive response to barbiturates, binding of pentobarbitone to plasma proteins from mice of different ages was measured by equilibrium dialysis in the presence of a standard concentration of the drug. The total plasma protein concentration was measured and found to be the same in both age groups. The plasma protein binding of pentobarbitone was found to correlate significantly with the plasma albumin concentration, which was lower in the older mice. However, there was no significant overall difference in pentobarbitone binding between old and young mice. Pretreatment of the mice with phenobarbitone for 21 days had no effect upon the capacity for plasma protein binding of pentobarbitone in either age group. Thus, it seems unlikely that the increased sensitivity of older mice to pentobarbitone can be explained in terms of altered plasma protein binding of the drug.

Penetration of nabumetone into inflammatory exudates in the rat.

The penetration of radioactivity into inflamed sites induced by subcutaneously implanted cotton pellets was studied in the rat after oral administration of [14C]nabumetone. Equilibration between inflamed site and plasma concentrations was slow, maximum concentrations in the pellet granuloma being later than those in the plasma. Nabumetone itself was found only in very low concentrations at the inflamed site and was not found in plasma. The major component (70%) of the radioactivity at both sites was the metabolite 6-methoxy-2-naphthylacetic acid, a compound which has anti-inflammatory properties. Elimination of radioactivity from the plasma and inflamed site was virtually complete within 24 h of dosing. Daily dosing with [14C]nabumetone confirmed that there was no progressive accumulation of radioactivity at the inflamed site.