Wonigeit K, Kohlhaw K, Winkler M, Schaefer O, Pichlmayr R
Klinik für Abdominal-und Transplantationschirurgie, Medizinische Hochschule Hannover, West Germany.
Transplant Proc. 1990 Jun;22(3):1305-11.
The parallel measurement of specific and nonspecific CyA levels by second generation radioimmunoassays based on monoclonal antibodies proved to be an effective procedure to monitor both parent CyA levels and the capacity to eliminate its metabolite. Using this monitoring procedure it could be shown that CyA-associated nephrotoxicity in the early course after liver transplantation is associated with two distinct patterns of blood level derangement. One pattern is characterized by increased parent drug levels, the other by an increased metabolite concentration resulting from severely disturbed CyA metabolite excretion. This raises the possibility that not only the parent drug but also some of its metabolites may exert nephrotoxic effects when present in excessively high concentrations. This finding provided the rationale for a therapeutic CyA-monitoring regimen taking into account both specific and nonspecific measurements. In liver transplant patients monitored according to this regimen and treated with quadruple immunosuppression the incidence and severity of CyA-associated nephrotoxicity was markedly reduced. The metabolite-associated type of nephrotoxicity was only found in patients with severely disturbed liver function.
基于单克隆抗体的第二代放射免疫分析法对环孢素（CyA）特异性和非特异性水平进行平行检测，被证明是监测母体CyA水平及其代谢产物清除能力的有效方法。使用这种监测方法可以发现，肝移植术后早期与CyA相关的肾毒性与两种不同的血药浓度紊乱模式有关。一种模式的特征是母体药物水平升高，另一种模式的特征是由于CyA代谢产物排泄严重紊乱导致代谢产物浓度升高。这就增加了一种可能性，即不仅母体药物，而且其某些代谢产物在浓度过高时也可能产生肾毒性作用。这一发现为同时考虑特异性和非特异性检测的CyA治疗监测方案提供了理论依据。按照该方案进行监测并接受四联免疫抑制治疗的肝移植患者中，与CyA相关的肾毒性的发生率和严重程度显著降低。与代谢产物相关的肾毒性类型仅在肝功能严重受损的患者中发现。
