Burckart G J, Jain A, Diven W, Venkataramanan R, Starzl T E
Clinical Pharmacokinetics Laboratory, University of Pittsburgh, Pennsylvania 15261.
Transplant Proc. 1990 Jun;22(3):1319-22.
The factors affecting CyA dosing and kinetics in LT patients are complex, and have been thoroughly investigated and reviewed. Plasma or WB CyA concentration monitoring remains the best method presently available for adjusting CyA dosage in LT patients in a timely manner. The availability of an FPIA assay for CyA has produced rapid drug analysis for transplant patient monitoring, but adds additional factors that must be considered in interpreting CyA concentrations. Liver dysfunction may disproportionately elevate CyA plasma or blood levels when analyzed by FPIA in relation to PC-RIA or HPLC, and adjustment of the therapeutic range or analysis by a more specific assay method may be necessary for dosage adjustment in these patients. The availability of a more specific antibody in an FPIA assay may avert these problems, as would the development of immunologic monitoring techniques that provide a global assessment of immune suppression produced by increasingly complex immunosuppressive regimens in LT patients.
影响肝移植(LT)患者环孢素A(CyA)给药剂量及药代动力学的因素复杂,且已得到充分研究和综述。血浆或全血CyA浓度监测仍是目前及时调整LT患者CyA剂量的最佳可用方法。用于CyA的荧光偏振免疫分析(FPIA)测定法的出现,实现了对移植患者的快速药物分析,但在解释CyA浓度时又增加了一些必须考虑的额外因素。与微粒体酶放射免疫分析(PC-RIA)或高效液相色谱法(HPLC)相比,当采用FPIA分析时,肝功能不全可能会使CyA的血浆或血液水平异常升高,对于这些患者,可能需要调整治疗范围或采用更特异的测定方法进行分析以调整剂量。FPIA测定法中更特异抗体的出现可能会避免这些问题,免疫监测技术的发展也可能会避免这些问题,该技术可全面评估LT患者中日益复杂的免疫抑制方案所产生的免疫抑制作用。