Ptachcinski R J, Venkataramanan R, Burckart G J, Gray J A, Van Thiel D H, Sanghvi A, Rosenthal J T
Department of Pharmacy Practice, University of Pittsburgh, School of Pharmacy, Pennsylvania.
J Clin Pharmacol. 1987 Mar;27(3):243-8. doi: 10.1002/j.1552-4604.1987.tb02193.x.
The pharmacokinetics of cyclosporine was studied in five healthy male volunteers following intravenous administration. The subjects received 2.1 mg/kg of cyclosporine as a two-hour intravenous infusion. Blood samples were collected over the subsequent 48 hours. Cyclosporine was extracted from whole blood and analyzed by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Following the intravenous infusion of cyclosporine, the drug exhibited multicompartmental behavior. The harmonic mean distribution half-life based on HPLC data was 0.45 hours, and the harmonic mean terminal disposition half-life was 6.2 hours. The clearance of cyclosporine based on HPLC cyclosporine concentrations was 3.9 mL/min/kg, and the volume of distribution at steady state of cyclosporine was 1.23 L/kg. Cyclosporine has a shorter half-life, lower clearance, and smaller Vss in healthy persons as compared to patient populations. The differences observed in the pharmacokinetics of cyclosporine in healthy persons as compared to patient populations may be due to differences in hematocrit, lipoprotein profiles, and/or concurrent drug therapy between the groups. Cyclosporine concentrations determined by RIA were consistently higher than those determined by HPLC, resulting in a significantly higher area under the blood concentration versus time curve and lower clearance rate for cyclosporine. We conclude that: (1) kinetic parameter estimates for cyclosporine are different in healthy individuals as compared with organ-transplant recipients, and (2) the kinetic parameters for cyclosporine are different, depending on the assay technique used.
在5名健康男性志愿者静脉注射环孢素后，对其药代动力学进行了研究。受试者接受2.1mg/kg的环孢素，静脉输注2小时。在随后的48小时内采集血样。从全血中提取环孢素，并通过高效液相色谱法（HPLC）和放射免疫分析法（RIA）进行分析。静脉输注环孢素后，该药物呈现多室行为。基于HPLC数据的调和平均分布半衰期为0.45小时，调和平均终末处置半衰期为6.2小时。基于HPLC环孢素浓度计算的环孢素清除率为3.9mL/min/kg，环孢素稳态分布容积为1.23L/kg。与患者群体相比，健康人中环孢素的半衰期更短、清除率更低且稳态分布容积更小。与患者群体相比，在健康人中环孢素药代动力学观察到的差异可能是由于两组之间血细胞比容、脂蛋白谱和/或同时进行的药物治疗存在差异。通过RIA测定的环孢素浓度始终高于通过HPLC测定的浓度，导致环孢素血药浓度-时间曲线下面积显著更高，清除率更低。我们得出以下结论：（1）与器官移植受者相比，健康个体中环孢素的动力学参数估计值不同；（2）环孢素的动力学参数因所使用的分析技术而异。
