Effects of vitamin E on the distribution and metabolism of nitrofurantoin in rats.

Previous studies have shown a significant increase in the pulmonary toxicity of nitrofurantoin (NF) in animals fed a diet lacking vitamin E. The authors have therefore examined the pharmacokinetics of NF in control and vitamin E-deficient male Sprague-Dawley rats. NF was rapidly absorbed following subcutaneous injection and was cleared from all tissues examined (blood, lung, liver and kidney) in a biphasic manner. Substantial metabolism of the drug was observed, and the disposition of NF metabolites was qualitatively similar to that of the parent compound. The most apparent difference between control and vitamin E-deficient animals was a significant increase in tissue metabolite levels 4-16 hr after treatment. Unchanged NF was also elevated in all tissues examined 16 hr after treatment in the vitamin E-deficient animals. Urinary excretion of NF and metabolites accounted for 68% of the total dose in control rats and 35% in vitamin E-deficient rats. This study illustrates a marked alteration in NF disposition in animals fed a diet lacking vitamin E when compared with controls. The observed alterations appear to be related to a decreased renal clearance of both NF and metabolites.