Effect of water deprivation and rehydration on gentamicin disposition in the rat

To study the effect of dehydration on gentamicin (G) kinetics, a group of rats was deprived of water for 4 days and then received a single i.v. dose of 3 mg/kg of G. Compared to control rats, the plasma and tissue concentration of G in dehydrated rats were increased and the elimination rate of the drug decreased. Higher G concentrations were found in plasma, spleen, renal cortex and medulla. These changes in G disposition consisted in a decrease of 33 and 22% of the apparent volume of distribution of the peripheral and central compartments, respectively, and, furthermore, in a decrease of 40% in the G apparent total body clearance. Another group of rats, after a similar period of water deprivation and i.v. administration of 3 mg/kg of G, were rehydrated with water or received a solution of NaCl and dextrose followed by water during 24 hr. In plasma and most tissues, rehydration did accelerate G washout without clear differences between the two modes of rehydration. It is concluded that a dehydration state will increase plasma and tissue G accumulation and might increase the risk of renal or ototoxicity. Rehydration will partially prevent and reverse G concentration. In a clinical setting, this event could very well occur. G tissue concentration cannot be predicted by changes in G plasma elimination half-life. The calculation of total body clearance and volume of distribution are necessary to predict the occurrence and estimate the extent of this tissue concentration.