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环孢素在骨髓移植受者中的药效学研究。三种检测方法的比较。

Pharmacodynamic studies of cyclosporine in marrow transplant recipients. A comparison of three assay methods.

作者信息

McGuire T R, Yee G C, Emerson S, Gmur D J, Carlin J

机构信息

Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.

出版信息

Transplantation. 1992 Jun;53(6):1272-5. doi: 10.1097/00007890-199206000-00021.

DOI:10.1097/00007890-199206000-00021
PMID:1604484
Abstract

We investigated the correlation between trough cyclosporine concentration in plasma measured by polyclonal fluorescence polarization immunoassay (FPIA) and polyclonal radioimmunoassay (RIA) or in whole blood measured by high-performance liquid chromatography (HPLC) and the risk of renal dysfunction or acute graft-versus-host disease in 29 patients undergoing allogeneic bone marrow transplantation for leukemia. The FPIA and RIA values were highly correlated (r = 0.93) and on the average CsA concentrations measured by FPIA were 1.56 times higher than those measured by RIA. Ten patients developed renal dysfunction and 10 developed grades II-IV acute GVHD. Although univariate analysis showed that plasma CsA concentrations measured by either FPIA or RIA were significantly correlated with renal dysfunction, the association was stronger with FPIA. Plasma CsA concentrations measured by FPIA but not RIA remained a significant risk factor for renal dysfunction in a multivariate relative risk model. Amphotericin therapy was significantly associated with renal dysfunction in the univariate analysis but not in the multivariate analysis. No significant associations were found between whole blood CsA or CsA M1 concentration, patients' age, gender, or CsA dose and the risk of renal dysfunction. None of the covariates analyzed significantly correlated with the development of acute GVHD. These data suggest that plasma CsA concentrations measured by nonspecific assays may more accurately correlate with renal dysfunction than whole-blood CsA concentrations measured by HPLC in marrow transplant recipients.

摘要

我们研究了通过多克隆荧光偏振免疫分析法(FPIA)和多克隆放射免疫分析法(RIA)测定的血浆中环孢素谷浓度之间的相关性,以及通过高效液相色谱法(HPLC)测定的全血中环孢素谷浓度与29例接受白血病异基因骨髓移植患者的肾功能不全或急性移植物抗宿主病风险之间的相关性。FPIA和RIA值高度相关(r = 0.93),FPIA测定的环孢素平均浓度比RIA测定的高1.56倍。10例患者出现肾功能不全,10例发生II-IV级急性移植物抗宿主病。单因素分析显示,FPIA或RIA测定的血浆环孢素浓度与肾功能不全显著相关,但FPIA的相关性更强。在多因素相对风险模型中,FPIA而非RIA测定的血浆环孢素浓度仍然是肾功能不全的显著危险因素。两性霉素治疗在单因素分析中与肾功能不全显著相关,但在多因素分析中并非如此。全血环孢素或环孢素M1浓度、患者年龄、性别或环孢素剂量与肾功能不全风险之间未发现显著相关性。分析的协变量均与急性移植物抗宿主病的发生无显著相关性。这些数据表明,在骨髓移植受者中,非特异性检测方法测定的血浆环孢素浓度可能比HPLC测定的全血环孢素浓度更准确地与肾功能不全相关。

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