Effects of Age on the Pharmacokinetics of Piroxicam in Rats

• Published in: Journal of pharmaceutical sciences 1993-03, Vol.82 (3), p.254-257
• Main Authors: Boudinot, Sally G., Funderburg, Eric D., Douglas Boudinot, F.
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Animals; Biological and medical sciences; Biological Availability; Bones, joints and connective tissue. Antiinflammatory agents; Injections, Intravenous; Liver - metabolism; Male; Medical sciences; Models, Biological; Pharmacology. Drug treatments; Piroxicam - blood; Piroxicam - pharmacokinetics; Protein Binding; Rats; Rats, Inbred F344
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600820307

This study examined the effects of age on the pharmacokinetics of piroxicam in rats. Two groups of rats, aged 5 and 24 months, were administered 1mg of piroxicam per kg intravenously, and blood samples were withdrawn for up to 120h. Protein binding studies, with pooled serum from each age group were also performed. Piroxicam concentrations were determined by HPLC analysis, and pharmacokinetic parameters were’ characterized by area-moment analysis. Plasma piroxicam concentrations declined in both age groups in a biexponential fashion, with half-lives of 5.9 ± 0.7h (mean ± SD) in the young rats and 30.6 ± 9.9h in the old rats. Total clearance in the young rats was 0.048 ± 0.012 L/h/kg, whereas that in the old rats was 0.021 ± 0.003 L/h/kg. The steady-state volume of distribution in the young rats was 0.42 ± 0.05 L/kg, and that in the old rats was 0.56 ± 0.10 L/kg. There was a statistically significant difference between these parameters calculated for each age group. Piroxicam is a highly plasma protein-bound drug; the fraction unbound in the young rats was determined to be 0.067 ± 0.022, and that in the old rats was determined to be 0.134 ± 0.065, or twice that in the young rats. Differences in protein binding were due, in part, to a 20% decreased albumin concentration in the old rats; however, there was also a decrease in the number of binding sites and/or the binding affinity with aging. Clearance of free drug in the young rats was 0.73 ± 0.18 L/h/kg, and that in the old rats was 0.15 ± 0.02 L/h/kg; the steady-state volumes of distribution for unbound drug were determined to be 6.27 ± 0.78 L/kg for the young rats and 4.18 ± 0.75 L/kg for the old rats. These differences were significantly different. Thus, piroxicam exhibited an age-related disposition in rats.