Kelly D W, Holder C L, Korfmacher W A, Slikker W
National Center for Toxicological Research, University of Arkansas for Medical Sciences, Jefferson, AR 72079-9502.
Drug Metab Dispos. 1990 Nov-Dec;18(6):1018-24.
The metabolism and elimination of methapyrilene (2-[(2-dimethylaminoethyl)-2-thenylamino]pyridine) were characterized after the iv administration of 0.7 mg/kg or 3.5 mg/kg methapyrilene HCl plus [14C]methapyrilene HCl to adult male Fischer-344 rats. Approximately 40% and 35% of the administered dose was excreted in the urine in the first 24 hr in the low and high dose groups, respectively, as determined by liquid scintillation spectrophotometry. Fecal excretion accounted for 38% and 44% of the administered dose in the first 24 hr in the low and high dose groups, respectively, as confirmed via combustion analysis. The 24-hr urinary metabolic products consisted of one major and five minor radiolabeled compounds. The major metabolite was isolated with reversed-phase HPLC and identified as methapyrilene N-oxide. This was accomplished by comparison of the chromatographic and mass spectral characteristics of this metabolite with that of authentic methapyrilene N-oxide. Methapyrilene and mono-N-desmethyl methapyrilene also were identified after isolation with reversed-phase HPLC and comparison of their mass spectral and/or chromatographic properties with those of authentic compounds. The plasma metabolic profile was essentially the same as the urinary profile. The elimination of methapyrilene from plasma occurred through a first-order process. The terminal plasma elimination t1/2 of methapyrilene did not increase with increasing doses (2.75 hr, 0.7 mg/kg; 2.81 hr, 3.5 mg/kg); thus, methapyrilene does not exhibit dose-dependent elimination over this 5-fold dose range.
给成年雄性Fischer-344大鼠静脉注射0.7mg/kg或3.5mg/kg盐酸美吡拉敏加[¹⁴C]盐酸美吡拉敏后，对美吡拉敏（2-[(2-二甲氨基乙基)-2-噻吩甲基氨基]吡啶）的代谢和消除情况进行了表征。通过液体闪烁分光光度法测定，低剂量组和高剂量组在前24小时内分别约有40%和35%的给药剂量经尿液排出。通过燃烧分析证实，低剂量组和高剂量组在前24小时内粪便排泄量分别占给药剂量的38%和44%。24小时尿液代谢产物由一种主要放射性标记化合物和五种次要放射性标记化合物组成。主要代谢产物通过反相高效液相色谱法分离，并鉴定为美吡拉敏N-氧化物。这是通过将该代谢产物的色谱和质谱特征与 authentic美吡拉敏N-氧化物的特征进行比较来完成的。用反相高效液相色谱法分离并将其质谱和/或色谱性质与 authentic化合物的性质进行比较后，也鉴定出了美吡拉敏和单-N-去甲基美吡拉敏。血浆代谢谱与尿液谱基本相同。美吡拉敏从血浆中的消除通过一级过程进行。美吡拉敏的终末血浆消除半衰期并不随剂量增加而增加（0.7mg/kg时为2.75小时；3.5mg/kg时为2.81小时）；因此，在这个5倍剂量范围内，美吡拉敏不表现出剂量依赖性消除。
