Statham C N, Minchin R F, Sasame H A, Kim S H, Boyd M R
Drug Metab Dispos. 1985 Sep-Oct;13(5):532-4.
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.
先前的研究表明，在喂食缺乏维生素E饮食的动物中，呋喃妥因（NF）的肺毒性显著增加。因此，作者研究了NF在对照和维生素E缺乏的雄性斯普拉格-道利大鼠体内的药代动力学。皮下注射后，NF迅速被吸收，并以双相方式从所有检测组织（血液、肺、肝和肾）中清除。观察到该药物有大量代谢，且NF代谢物的处置在质量上与母体化合物相似。对照动物和维生素E缺乏动物之间最明显的差异是治疗后4至16小时组织代谢物水平显著增加。在维生素E缺乏的动物中，治疗16小时后，所有检测组织中未变化的NF也升高。NF及其代谢物的尿排泄在对照大鼠中占总剂量的68%，在维生素E缺乏的大鼠中占35%。本研究表明，与对照相比，喂食缺乏维生素E饮食的动物中NF的处置有显著改变。观察到的改变似乎与NF及其代谢物的肾清除率降低有关。
