Administration time-dependent change in the effect of spironolactone in aged rats

We have previously demonstrated that the natriuretic effect of spironolactone, a competitive antagonist of mineralocorticoid, varies with its administration time in young rats. The present study was undertaken to examine the influence of aging on chronopharmacological profiles of the agent. Spironolactone (10 and 50 mg/kg) was given orally at 12 am or 12 pm in young (12 weeks old) and aged (28 months old) Wistar rats. The 8-hour urine was collected after each administration, and the urinary sodium excretion was determined. The urinary sodium excretion increased dose-dependently following spironolactone in the young and aged groups of rats. The increments in this parameter in the 12 pm trial were significantly greater than those of the 12 am trial in the young rats. However, such an administration time-dependent difference in the effect of spironolactone was diminished and did not reach statistical significance in the aged animals. These results suggest that the mode of the administration time-dependent change in the effect of spironolactone is altered with age.