Cyclosporine kinetics in healthy volunteers.
Cyclosporine kinetics in healthy volunteers.
复制标题
健康志愿者中的环孢菌素动力学。
DOI：
10.1002/j.1552-4604.1987.tb02193.x
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发表时间：
1987
影响因子：
2.9
通讯作者：
Rosenthal,JT
中科院分区：
文献类型：
--
作者：
Ptachcinski,RJ;Venkataramanan,R;Burckart,GJ;Gray,JA;VanThiel,DH;Sanghvi,A;Rosenthal,JT
研究了环孢素在5名健康男性志愿者静脉给药后的药代动力学。受试者接受2.1 mg/kg环孢素2小时静脉输注。在随后的48小时内采集血液样本。从全血中提取环孢素，采用高效液相色谱法（HPLC）和放射免疫分析法（RIA）进行分析。静脉输注环孢素后，药物表现出多房室行为。基于HPLC数据的调和平均分布半衰期为0.45 h，调和平均终端配置半衰期为6.2 h。HPLC法测定环孢素浓度对环孢素的清除率为3.9 mL/min/kg，稳态分布体积为1.23 L/kg。与患者群体相比，环孢素的半衰期较短，清除率较低，健康人群的Vssin较小。健康人与患者之间环孢素药代动力学的差异可能是由于两组之间红细胞压积、脂蛋白谱和/或同时药物治疗的差异。RIA法测定的环孢素浓度始终高于HPLC法测定的环孢素浓度，导致环孢素血药-时间曲线下面积明显增大，清除率较低。我们得出结论：(1)与器官移植接受者相比，健康个体环孢素的动力学参数估计值是不同的；(2)环孢素的动力学参数是不同的，取决于所使用的检测技术。
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 Vssin 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.