Bozkurt F, Stierle H, Schollmeyer P, Keller E
Clin Nephrol. 1987 Jul;28(1):10-4.
Cyclosporine (Cy) dose-response kinetics were studied in 8 renal failure patients awaiting kidney transplantation. All patients received a single oral dose of Cy (7 mg/kg). Blood samples were drawn frequently before and until 4 days after Cy administration. Cy blood levels were measured by radioimmunoassay (RIA). OKT3-induced in vitro proliferation of simultaneously isolated lymphocytes was determined by H3-thymidine incorporation. T cell subpopulations were enumerated using a peroxidase-antiperoxidase method. Mean Cy blood level reached its peak (Cmax = 1,466 +/- 186 ng/ml) at 4 to 6 hours, the elimination half life (t1/2) measured 31 +/- 7.2 hours. The T4/T8 cell ratio did not change during the study, the total numbers of T3, T4 and T8 positive lymphocytes showed well known circadian variations without an apparent influence of Cy. There was a strong relationship between Cy blood levels and the inhibition of in vitro lymphocyte proliferation (y = 21.1 -0.007x, r = -0.91, p less than 0.001). With decreasing Cy blood concentrations the proliferative potency of lymphocytes was restored without delay in time. In conclusion circulating T cell subpopulations are not influenced by a single dose of Cy, the strong correlation between drug levels and the inhibition of lymphoproliferation suggest that RIA derived Cy blood concentrations are a valuable tool for estimating immunosuppression.
对8名等待肾移植的肾衰竭患者进行了环孢素（Cy）剂量反应动力学研究。所有患者均接受单次口服剂量的Cy（7mg/kg）。在给药前及给药后直至4天频繁采集血样。采用放射免疫分析法（RIA）测定Cy血药浓度。通过3H-胸腺嘧啶掺入法测定OKT3诱导的同时分离的淋巴细胞的体外增殖。使用过氧化物酶-抗过氧化物酶方法计数T细胞亚群。Cy血药浓度均值在4至6小时达到峰值（Cmax = 1466±186ng/ml），消除半衰期（t1/2）为31±7.2小时。研究期间T4/T8细胞比值未发生变化，T3、T4和T8阳性淋巴细胞总数呈现出众所周知的昼夜变化，未受Cy的明显影响。Cy血药浓度与体外淋巴细胞增殖抑制之间存在很强的相关性（y = 21.1 - 0.007x，r = -0.91，p < 0.001）。随着Cy血药浓度降低，淋巴细胞的增殖能力立即恢复。总之，循环T细胞亚群不受单次剂量Cy的影响，药物浓度与淋巴细胞增殖抑制之间的强相关性表明，RIA测定的Cy血药浓度是评估免疫抑制的有价值工具。
