Christians U, Kohlhaw K, Budniak J, Bleck J S, Schottmann R, Schlitt H J, Almeida V M, Deters M, Wonigeit K, Pichlmayr R
Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, FRG.
Eur J Clin Pharmacol. 1991;41(4):291-6. doi: 10.1007/BF00314954.
The pattern of metabolites of ciclosporin in blood and 24 h-urine of 58 liver graft recipients was routinely monitored by HPLC from transplantation until discharge from hospital. Liver function and ciclosporin metabolite pattern in patients with an uncomplicated clinical course and in those with cholestasis or acute rejection were compared. During cholestasis M19 and M1A, and during acute rejection M19, in blood were significantly elevated compared to the control group. Blood M19 was significantly correlated with bilirubin concentration and gamma-glutamyl transferase activity in serum, and M1A with the serum bilirubin concentration. Analysis of the metabolite pattern over the observation period showed higher concentrations of M19 and M1A in blood from patients with cholestasis and acute rejection than in the control group; concentrations were lower in the rejection group than in the cholestasis group. The metabolite pattern in 24 h-urine showed similar alterations in ciclosporin metabolite pattern to those in blood. Cholestasis and rejection shift the ciclosporin metabolite pattern in blood and urine to higher concentrations of M19 and M1A, whereas the concentrations of other metabolites and ciclosporin were not significantly affected.
从移植到出院期间，通过高效液相色谱法（HPLC）对58例肝移植受者血液和24小时尿液中环孢素的代谢物模式进行常规监测。比较了临床过程无并发症的患者以及出现胆汁淤积或急性排斥反应的患者的肝功能和环孢素代谢物模式。在胆汁淤积期间，血液中的M19和M1A以及在急性排斥反应期间血液中的M19与对照组相比显著升高。血液中的M19与血清胆红素浓度和γ-谷氨酰转移酶活性显著相关，而M1A与血清胆红素浓度相关。对观察期内代谢物模式的分析表明，胆汁淤积和急性排斥反应患者血液中M19和M1A的浓度高于对照组；排斥反应组的浓度低于胆汁淤积组。24小时尿液中的代谢物模式显示环孢素代谢物模式与血液中的变化相似。胆汁淤积和排斥反应使血液和尿液中环孢素的代谢物模式向更高浓度的M19和M1A转变，而其他代谢物和环孢素的浓度未受到显著影响。
