Effect of water deprivation on aspirin disposition kinetics.

Temporary water deprivation results in serious stress causing significant physiological, hormonal, and enzymatic changes in the body which can affect the disposition kinetics, toxicity, and activity of drugs. This study attempts to recognize the effect of water deprivation on drug disposition kinetics using aspirin. No significant effects were noted following 36-hr water deprivation in rats on the metabolism of aspirin; there was also no effect of heparinization on aspirin disposition kinetics. The disposition of salicylic acid, however, was altered significantly, with the half-life increased by approximately 72% concomitant with decreased total body clearance. The effect of two dose levels, 5 and 10 mg/kg, was also studied to elucidate nonlinearity in the disposition kinetic model. Almost complete urinary recovery of aspirin was obtained in the intact form or as metabolites. At the 10-mg/kg dose, the fraction of salicyluric acid excreted decreased significantly compared with the 5-mg/kg dose. However, the effect of water deprivation was uniform at the two dose levels without any effect on the excretion of salicyluric acid. It is suggested that, in view of the significant changes in the disposition characteristics of salicylates with water deprivation, due care must be exercised in adjusting doses giving proper consideration to body hydration levels.