Burckart G J, Starzl T E, Venkataramanan R, Hashim H, Wong L, Wang P, Makowka L, Zeevi A, Ptachcinski R J, Knapp J E
Transplant Proc. 1986 Dec;18(6 Suppl 5):46-9.
Quantitative and qualitative studies of cyclosporine and its metabolites were performed on human bile from liver transplant and liver disease patients. The concentration of CsA in bile is higher in patients with normal liver function than in those with poor liver function but in neither case could account for more than 2% of an absorbed dose of CsA. Although concentrations of CsA plus metabolites in bile measured by RIA were 18 to 36 times higher than HPLC concentrations, they accounted for less than 50% of an absorbed CsA dose. By means of mass spectrometry and HPLC retention times of known metabolites, peaks equivalent to the previously isolated CsA M8, M13, M17, M1, M18, and M21 of Maurer et al were found in the ether extracts of bile. Future studies should not only concentrate on the pharmacologic and toxicologic effects of the metabolites but should also accurately quantitate these compounds in blood, plasma, urine, and bile.
对肝移植患者和肝病患者的人胆汁进行了环孢素及其代谢产物的定量和定性研究。肝功能正常的患者胆汁中环孢素A（CsA）的浓度高于肝功能差的患者，但在这两种情况下，其含量均不超过吸收剂量的2%。尽管放射免疫分析（RIA）测定的胆汁中CsA及其代谢产物的浓度比高效液相色谱（HPLC）测定的浓度高18至36倍，但它们占吸收的CsA剂量的比例不到50%。通过质谱分析和已知代谢产物的HPLC保留时间，在胆汁的乙醚提取物中发现了与Maurer等人先前分离出的CsA M8、M13、M17、M1、M18和M21相当的峰。未来的研究不仅应关注代谢产物的药理和毒理作用，还应准确测定血液、血浆、尿液和胆汁中这些化合物的含量。
