Mulder G J
Fed Proc. 1986 Jul;45(8):2229-34.
Sulfation of phenols and similar low-molecular-weight substrates in the rat in vivo is a rather complex process. Besides enzyme kinetic parameters, cosubstrate availability (indirectly measured by serum sulfate concentration) and competition with glucuronidation also play a role. For some substrates extensive extrahepatic sulfation occurs, accounting for more than 50% of the total-body sulfation capacity. However, the hepatic contribution may be under-estimated when drugs are administered into the hepatic portal vein, because saturation of hepatic metabolism may occur under those conditions. Inside the liver, sulfation is located primarily in zone 1, the periportal area. This can be shown in the single-pass perfused rat liver by perfusion in either the normal or retrograde flow direction. In the rat sulfate conjugates are eliminated preferentially in urine, whereas glucuronides are excreted to a high extent in bile. Therefore, it is important to collect both bile and urine in the characterization of pharmacokinetics of conjugation in vivo. Selective inhibition of sulfation by pentachlorophenol and 2,6-dichloro-4-nitrophenol facilitates studies of the role of sulfation in elimination of its substrates, and the competition between sulfation and glucuronidation for the same substrate.
大鼠体内酚类及类似低分子量底物的硫酸化是一个相当复杂的过程。除了酶动力学参数外，共底物可用性（通过血清硫酸盐浓度间接测量）以及与葡萄糖醛酸化的竞争也起作用。对于某些底物，会发生广泛的肝外硫酸化，占全身硫酸化能力的50%以上。然而，当药物经肝门静脉给药时，肝脏的贡献可能被低估，因为在这些条件下可能会发生肝脏代谢饱和。在肝脏内部，硫酸化主要位于1区，即门静脉周围区域。这可以通过在正常或逆行血流方向灌注的单通道灌注大鼠肝脏中得到证明。在大鼠中，硫酸盐结合物优先经尿液排出，而葡萄糖醛酸结合物则大量经胆汁排泄。因此，在体内结合物药代动力学特征研究中同时收集胆汁和尿液很重要。五氯苯酚和2,6-二氯-4-硝基苯酚对硫酸化的选择性抑制有助于研究硫酸化在其底物消除中的作用，以及硫酸化和葡萄糖醛酸化对同一底物的竞争。
