The metabolism, pharmacokinetics, tissue distribution, and excretion of L-N6-(1-iminoethyl)lysine-5-tetrazole-amide (L-NIL-TA), a selective inducible NO synthase (iNOS) inhibitor, were investigated in rats. [(14)C]L-NIL-TA is extensively metabolized after either oral or IV administration with a minor amount (<1%) excreted as the prodrug. L-NIL-TA is metabolized via a single hydrolysis pathway to form the active drug, L-N6-(1-iminoethyl)lysine (L-NIL). The oxidative deamination of 2-amino group of L-NIL forms a 2-keto metabolite (M5), which further loses carbon dioxide to yield a carboxylic acid metabolite (M6). Acetylation of L-NIL and M5 resulted in the formations of metabolites M7 and M4, respectively. Complete recovery of the radioactive dose was achieved after either oral (91.2% in urine and 4.66% in feces) and IV (99.3% in urine and 5.11% in feces) administration. L-NIL-TA-related material was extensively distributed to the tissues, with the highest concentration of radioactivity being found in muscle. Maximal concentration of radioactivity was reached between 0.5 and 1 h post-dose in the majority of tissues, with the exception of muscle and skin where the maximal concentrations were achieved at 8 h post-dose.

中文翻译：

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选择性iNOS抑制剂L-N6-（1-亚氨基乙基）赖氨酸-5-四唑-酰胺的配置和药代动力学

在大鼠中研究了选择性诱导型NO合酶（iNOS）抑制剂L-N6-（1-亚氨基乙基）赖氨酸-5-四唑-酰胺（L-NIL-TA）的代谢，药代动力学，组织分布和排泄。口服或静脉给药后，[（14）C] L-NIL-TA被广泛代谢，少量（<1％）作为前药排泄。L-NIL-TA通过单个水解途径代谢，形成活性药物L-N6-（1-亚氨基乙基）赖氨酸（L-NIL）。L-NIL的2-氨基氧化脱氨基形成2-酮代谢物（M5），其进一步损失二氧化碳，生成羧酸代谢物（M6）。L-NIL和M5的乙酰化分别导致代谢产物M7和M4的形成。口服（尿液为91.2％，粪便为4.66％）和静脉输液（尿液为99.3％和5）后，放射性剂量完全恢复。11％的粪便）管理。L-NIL-TA相关材料广泛分布于组织中，在肌肉中发现的放射性浓度最高。在大多数组织中，放射性最大浓度在给药后0.5到1小时之间达到，但肌肉和皮肤除外，后者在给药后8小时达到最大放射性浓度。