Neef K, Jonkman J H, Meijer D K
J Pharm Sci. 1978 Aug;67(8):1147-50. doi: 10.1002/jps.2600670832.
The disappearance from plasma and the excretion in bile of the monoquaternary thiazinamium (administered as the iodide) and one of its polar metabolites, thiazinamium sulfoxide (also administered as the iodide), were studied in the rat after intravenous injection to obtain more information on hepatic transport mechanisms for organic cations. Both compounds exhibited an extremely rapid plasma disappearance, partly due to a rapid liver uptake. After injection of thiazinamium iodide and thiazinamium sulfoxide iodide, 36 and 47%, respectively, of the administered dose were excreted in bile during 1 hr. TLC analysis of the bile showed at least two unidentified polar metabolites in addition to thiazinamium sulfoxide and only 3.8% unchanged thiazinamium after administration of thiazinamium iodide. The same metabolites were found after injection of thiazinamium sulfoxide iodide. Urinary excretion and intestinal secretion were 18 and 12%, respectively, for thiazinamium sulfoxide iodide and 27 and 9%, respectively, of the dose for thiazinamium iodide. It is concluded that, in spite of unequal physicochemical features, thiazinamium iodide and thiazinamium sulfoxide iodide differ only slightly in hepatic uptake and metabolism.
为了获取更多关于有机阳离子肝脏转运机制的信息，研究了大鼠静脉注射单季铵噻嗪铵（以碘化物形式给药）及其一种极性代谢物亚砜噻嗪铵（也以碘化物形式给药）后，它们从血浆中的消失情况以及在胆汁中的排泄情况。两种化合物在血浆中的消失都极快，部分原因是肝脏摄取迅速。注射碘噻嗪铵和碘亚砜噻嗪铵后，在1小时内分别有36%和47%的给药剂量经胆汁排泄。胆汁的薄层色谱分析表明，除了亚砜噻嗪铵外，至少还有两种未鉴定的极性代谢物，注射碘噻嗪铵后只有3.8%的噻嗪铵未发生变化。注射碘亚砜噻嗪铵后也发现了相同的代谢物。碘亚砜噻嗪铵的尿排泄和肠道分泌分别为18%和12%，碘噻嗪铵的剂量分别为27%和9%。得出的结论是，尽管碘噻嗪铵和碘亚砜噻嗪铵的物理化学特性不同，但它们在肝脏摄取和代谢方面仅略有差异。
