Effects of age and sex on XXXX disposition.

@entity1 @entity5230
@entity5230 kinetics were studied after a single, oral, 20-mg capsule was taken by 12 young (six @entity1 , six @entity1 ) and 13 elderly (seven @entity1 , six @entity1 ) healthy subjects. Plasma samples were drawn for 216 hr after dosing. Plasma protein binding was studied in vitro by equilibrium dialysis and @entity5230 concentrations were measured by HPLC with ultraviolet detection. The apparent volume of distribution was smaller in elderly @entity1 (7.8 +/- 0.4 l) than in young @entity1 (11.3 +/- 0.3 l) and elderly @entity1 (10.8 +/- 0.8 l). There were no such differences when the apparent volume of distribution was normalized for total body weight. There was a strong correlation between total body weight and apparent volume of distribution in all subjects (r = 0.83). Plasma protein binding of @entity5230 ranged from 98.90% to 99.54% bound and was not affected by age or sex. @entity5230 body clearance in elderly @entity1 (0.026 +/- 0.002 ml/min/kg) was approximately 33% lower than in young @entity1 (0.039 +/- 0.003 ml/min/kg). This difference was reflected in different t1/2s of 61.7 and 44.9 hr. Predicted steady-state plasma @entity5230 concentrations were 5.7 micrograms/ml in young @entity1 , 5.4 micrograms/ml in young @entity1 , 5.7 micrograms/ml in elderly @entity1 , and 9.3 micrograms/ml in elderly @entity1 . The high value in elderly @entity1 results from the lower @entity5230 body clearance and total body weight. Our data suggest that healthy elderly @entity1 eliminate @entity5230 at a slower rate than healthy young @entity1 . The clinical significance of these data needs to be assessed in @entity1 .
