Atkinson K, Britton K, Biggs J
J Clin Pathol. 1984 Oct;37(10):1167-71. doi: 10.1136/jcp.37.10.1167.
In patients receiving cyclosporin to minimise graft versus host disease after allogeneic bone marrow transplantation, whole blood cyclosporin concentration was roughly twice the serum concentration when blood was separated at 37 degrees C. In turn, blood separation at 37 degrees C resulted in a doubling of serum cyclosporin concentration compared with separation at room temperature. In vitro studies showed that the latter phenomenon was due to a temperature dependent partitioning of cyclosporin between plasma and red cells, such that increased cyclosporin was taken up from the serum into red cells at room temperature. Increasing delay in separation of patient blood (at either temperature) resulted in a gradually increasing cyclosporin serum concentration. Further in vitro studies showed that a distribution equilibrium between blood components was reached within 30 min incubation. Red cell uptake of cyclosporin was saturable at an incubation concentration of greater than 4 microgram/ml, while plasma and mononuclear cells showed a linear uptake to 7 micrograms/ml. The cellular cyclosporin content of a mononuclear cell was roughly 1000 times greater than that of an erythrocyte. For clinical monitoring we recommend the measurement of cyclosporin concentration either in whole blood or in serum separated at 37 degrees C without delay after venepuncture.
在接受环孢素以尽量减少异基因骨髓移植后移植物抗宿主病的患者中,当血液在37℃下分离时,全血中环孢素浓度约为血清浓度的两倍。反过来,与在室温下分离相比,在37℃下分离血液导致血清环孢素浓度增加一倍。体外研究表明,后一种现象是由于环孢素在血浆和红细胞之间的温度依赖性分配,使得在室温下血清中的环孢素增加被红细胞摄取。患者血液分离延迟增加(在任一温度下)导致环孢素血清浓度逐渐增加。进一步的体外研究表明,在孵育30分钟内血液成分之间达到分布平衡。环孢素在红细胞中的摄取在孵育浓度大于4微克/毫升时达到饱和,而血浆和单核细胞则显示线性摄取至7微克/毫升。单核细胞的细胞内环孢素含量大约比红细胞高1000倍。对于临床监测,我们建议在静脉穿刺后立即测量全血或在37℃下分离的血清中环孢素浓度。