Bleck J S, Schlitt H J, Christians U, Thiesemann C, Strohmeyer S, Schottmann R, Kohlhaw K, Wonigeit K, Sewing K F
Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover, BRD.
Pharmacology. 1989;39(3):160-4. doi: 10.1159/000138593.
Renal elimination of the immunosuppressant ciclosporin is virtually unknown. Therefore, in 17 renal allograft recipients under steady-state conditions we studied the urinary excretion of ciclosporin and 17 of its metabolites in blood and 24-hour urine. Patients with liver dysfunction or treated with drugs potentially influencing the metabolism and elimination of ciclosporin were excluded from the study. Ciclosporin and its metabolites were measured by HPLC. Metabolite but not ciclosporin excretion was strongly correlated with creatinine clearance. Metabolites 18 and 26 (beta, epsilon-cyclic metabolite) were rarely found in blood but were excreted in considerable amounts in urine. Approximately 3% of the administered dose of ciclosporin per day undergoes renal elimination in unchanged form or as metabolites investigated. The data suggest glomerular filtration of ciclosporin metabolites, a difference in the rate of elimination between ciclosporin and the metabolites and some kind of metabolism or active transport mechanism for metabolites in the kidney.
免疫抑制剂环孢素经肾脏消除的情况实际上鲜为人知。因此，我们对17例处于稳态的肾移植受者进行了研究，测定他们血液中环孢素及其17种代谢产物以及24小时尿液中的排泄情况。肝功能不全或接受可能影响环孢素代谢和消除的药物治疗的患者被排除在研究之外。环孢素及其代谢产物通过高效液相色谱法进行测定。代谢产物而非环孢素的排泄与肌酐清除率密切相关。代谢产物18和26（β，ε-环化代谢产物）在血液中很少发现，但在尿液中有大量排泄。每天给予的环孢素剂量中约3%以未改变的形式或作为所研究的代谢产物经肾脏消除。数据表明环孢素代谢产物存在肾小球滤过，环孢素与其代谢产物的消除速率存在差异，并且肾脏中存在某种代谢或代谢产物的主动转运机制。
