Effects of age and sex on piroxicam disposition

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Abstract
Piroxicam kinetics were studied after a single, oral, 20-mg capsule was taken by 12 young (6 women, 6 men) and 13 elderly (7 women, 6 men) healthy subjects. Plasma samples were drawn for 216 h after dosing. Plasma protein binding was studied in vitro by equilibrium dialysis and piroxicam concentrations were measured by HPLC [high performance liquid chromatography] with ultraviolet detection. The apparent volume of distribution was smaller in elderly women (7.8 .+-. 0.4 l) than in young men (11.3 .+-. 0.3 l) and elderly men (10.8 .+-. 0.8 l). There were no such differences when the apparent volume of distribution was normalized for total body wt. There was a strong correlation between total body wt and apparent volume of distribution in all subjects (r = 0.83). Plasma protein binding of piroxicam ranged from 98.90%-99.54% bound and was not affected by age or sex. Piroxicam body clearance in elderly women (0.026 .+-. 0.002 ml/min per kg) was approximately 33% lower than in young women (0.039 .+-. 0.003 ml/min per kg). This difference was reflected in different t1/2 [half-life] of 61.7 and 44.9 h. Predicted steady-state plasma piroxicam concentrations were 5.7 .mu.g/ml in young women, 5.4 .mu.g/ml in young men, 5.7 .mu.g/ml in elderly men and 9.3 .mu.g/ml in elderly women. The high value in elderly women results from the lower piroxicam body clearance and total body wt. Healthy elderly women eliminate piroxicam at a slower rate than healthy young women. The clinical significance of the data needs to be assessed in patients.