Cyclosporine plasma unbound fraction in heart and lung transplantation recipients
Cyclosporine plasma unbound fraction in heart and lung transplantation recipients
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DOI：
10.1097/00007691-199902000-00003
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发表时间：
1999-02-01
影响因子：
2.5
通讯作者：
Brown, K
中科院分区：
文献类型：
--
作者：
Akhlaghi, F;Ashley, J;Brown, K
为了研究心脏、心肺和肺移植受者中环孢素未结合分数 (f(U)) 的变异性，通过平衡透析离体测定血浆中的环孢素 f(U)。在一项回顾性研究中，从 89 名心脏 (86%)、肺 (9%) 和心肺 (5%) 移植患者中获取了 260 个血浆样本（每位患者 7 个）。环孢菌素的未结合分数 (x100) 范围为 0.52% 至 3.94%，总体平均值为 1.53% +/- 0.375% (SD)。个体患者的平均未结合百分比范围为 0.71% 至 1.98%，患者间差异为 2.8 倍。在心脏移植受者（66 名患者）中，在更严重的排斥反应期间（需要抗排斥治疗（心内膜心肌活检结果为 3a 级及以上）），f(U) 值显着低于无排斥反应（0 级）或 la 级排斥反应期间的 f(U) 值 (p < 0.01)。 f(U) 的值不随器官移植（p = 0.35）或器官衰竭的病因（p = 0.32）而变化。环孢素 f(U) 与患者年龄呈负相关 (r = -0.18, p < 0.05)。未观察到 f(U) 与血液生化和细胞学指标之间的相关性。然而，高胆固醇血症移植受者 (1.37 +/- 0.52%) 的 f(U) 显着低于 (p < 0.01)，而正常胆固醇血症患者 (1.60 +/- 0.63%) 则较低。给予辛伐他汀导致平均 f(U) 从 1.40 +/- 0.09%) 显着增加至 1.82 +/- 0.13%（配对 t 检验，n = 13；p < 0.01）。在接受酮康唑治疗的患者中，f(U) 与对照组没有差异。这些发现表明环孢素f(U)的水平可能是环孢素免疫抑制活性的重要决定因素。此外，f(U)的变化可能与血清脂蛋白的浓度密切相关。因此，解释环孢素监测结果需要考虑患者的血脂状况。
To investigate the variability in the unbound fraction (f(U)) of cyclosporine in recipients of heart, heart-lung, and lung transplantation, cyclosporine f(U) was determined ex vivo in plasma by equilibrium dialysis. In a retrospective study, 260 samples of plasma tone to seven per patient) were obtained from 89 heart (86%), lung (9%), and heart-lung (5%) transplant patients. The unbound fraction (x100) of cyclosporine ranged from 0.52% to 3.94%, with an overall mean of 1.53% +/- 0.375% (SD). The mean percentage unbound for individual patients ranged from 0.71% to 1.98%, giving a 2.8-fold interpatient variation. In heart transplant recipients (66 patients), the values of f(U) were significantly lower (p < 0.01) during more severe rejection episodes, which required antirejection treatment (endomycardial biopsy result of grade 3a and higher) than in the absence of rejection (grade 0) or during grade la rejections. The value of f(U) did not vary with organ transplanted (p = 0.35) or etiology of organ failure (p = 0.32). Cyclosporine f(U) was negatively correlated with the age of the patient (r = -0.18, p < 0.05). Correlations were not observed between f(U) and blood biochemical and cytologic indices. However, f(U) was significantly lower (p < 0.01) in hypercholesterolemic transplant recipients (1.37 +/- 0.52%) than in normocholesterolemic patients (1.60 +/- 0.63%). Administration of simvastatin resulted in a significant increase in the mean f(U) from 1.40 +/- 0.09%) to 1.82 +/- 0.13% (paired t test, n = 13; p < 0.01). In patients who received ketoconazole, f(U) was not different from controls. These findings suggest that the level of cyclosporine f(U) may be an important determinant of immunosuppressive activity of cyclosporine. Moreover, the variation in f(U) could be strongly related to the concentration of serum Lipoproteins; interpretation of the results of cyclosporine monitoring thus requires consideration of the lipidemic status of the patient.