Buttar H S, Wong L T, Moffatt J H
Arch Int Pharmacodyn Ther. 1978 Sep;235(1):9-18.
The effect of isoniazid (INH, 0,5, 10 or 20 mg/kg; p.o.) on the metabolic disposition of 14C-diphenylhydantoin (DPH, 50 mg/kg; i.v.) was studied in rats for 5 hours. The disappearance rate of 14C from the blood was similar up to 2 hr, whereas at 3 hr the levels of 14C were significantly higher in 10 and 20 mg/kg INH-treated rats than the controls. While the urinary excretion remained virtually unaltered, the fecal excretion of 14C was significantly reduced in the presence of INH. Increasing doses of INH caused a corresponding increase in the concentration of 14C in the blood, plasma, liver, kidney, lung, brain, skeletal muscle, fat, heart, tests and spleen. At the end of 5 hr, about 74% of the radioactivity was present as unmetabolized DPH in the plasma of control animals; this was increased significantly in a dose-related manner by INH, reaching a concentration of 93% at the highest doses of INH administered. The results suggest that the INH-induced elevation of DPH-derived 14C in plasma and its marked accumulation in other tissues is due to inhibition of both the p-hydroxylation of DPH and the glucuronidation of its metabolites.
在大鼠中研究了异烟肼（INH，0、5、10或20mg/kg；口服）对14C - 二苯乙内酰脲（DPH，50mg/kg；静脉注射）代谢处置的影响，持续5小时。在2小时内，14C从血液中的消失速率相似，而在3小时时，10mg/kg和20mg/kg INH处理组大鼠血液中的14C水平显著高于对照组。虽然尿排泄基本未改变，但在INH存在下，14C的粪便排泄显著减少。INH剂量增加导致血液、血浆、肝脏、肾脏、肺、脑、骨骼肌、脂肪、心脏、睾丸和脾脏中14C浓度相应增加。在5小时结束时，对照动物血浆中约74%的放射性以未代谢的DPH形式存在；INH以剂量相关的方式显著增加了这一比例，在给予最高剂量INH时达到93%的浓度。结果表明，INH引起血浆中DPH衍生的14C升高及其在其他组织中的显著蓄积是由于抑制了DPH的对羟基化及其代谢产物的葡萄糖醛酸化。
