Webber I R, Peters W H, Back D J
Department of Pharmacology and Therapeutics, University of Liverpool.
Br J Clin Pharmacol. 1992 Jun;33(6):661-4. doi: 10.1111/j.1365-2125.1992.tb04098.x.
The in vitro metabolism of the immunosuppressant cyclosporin (CsA) by human gastrointestinal mucosal microsomes has been studied. Macroscopically normal intestinal (n = 4) and liver (n = 2) tissue was obtained from kidney transplant donors, and microsomes prepared. Intestinal metabolism was most extensive with duodenal protein (15% conversion to metabolites M1/M17 after 2 h incubation at 37 degrees C; metabolite measurement by h.p.l.c). Western blotting confirmed the presence of P-4503A (enzyme subfamily responsible for CsA metabolism) in duodenum and ileum tissue, but not in colon tissue. The results of this study indicate that the gut wall may play a role in the first-pass metabolism of CsA, and could therefore be a contributory factor to the highly variable oral bioavailability of CsA.
已对人胃肠道黏膜微粒体对免疫抑制剂环孢素（CsA）的体外代谢进行了研究。从肾移植供体获取了宏观正常的肠道（n = 4）和肝脏（n = 2）组织，并制备了微粒体。肠道代谢最为广泛，十二指肠蛋白在37℃孵育2小时后有15%转化为代谢物M1/M17（通过高效液相色谱法测定代谢物）。蛋白质印迹法证实十二指肠和回肠组织中存在P - 4503A（负责CsA代谢的酶亚家族），但结肠组织中不存在。本研究结果表明，肠壁可能在CsA的首过代谢中起作用，因此可能是导致CsA口服生物利用度高度可变的一个因素。
