Tafazoli Ali, Dadashzadeh Simin, Mehdizadeh Mahshid, Parkhideh Sayeh, Tavakoli-Ardakani Maria
Student' Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2019 Fall;18(Suppl1):302-314. doi: 10.22037/ijpr.2020.112111.13539.
Allogeneic hematopoietic stem cell transplantation (AHSCT) is a major method of treatment for different hematologic and congenital disease. Graft versus host disease (GvHD) is a life-threatening adverse effect of AHSCT. Cyclosporine is the most important and common agent for GvHD prophylaxis. Because of variable and unpredictable pharmacokinetics of cyclosporine that produces different responses in each patients group and clinical setting, there are still lots of uncertainties about its optimal method of administration and monitoring of this drug. Frequent blood samples in eight different times were taken for cyclosporine quantification in twenty AHSCT recipients and pharmacokinetic parameters determined in both intravenous (IV) and oral administration and monitoring parameters assessed accordingly. Of pharmacokinetic parameters mean ± SD area under concentration - time curve (AUC), clearance, and half-life were estimated to be 5492 ± 1596 ng.h/mL, 19.44 ± 6.61 L/h, and 11.8 ± 5.4 h for IV and 7637.7 ± 2739.8 ng.h/mL, 19.42 ± 6.62 L/h, and 11.16 ± 5.9 h for oral administration, respectively. Appropriate oral to intravenous dosing ratio found to be about 1.6. Of monitoring parameters, C h and C showed the highest coefficient of determination for regression between single points and total area under curve. Evaluation of pharmacokinetic parameters derived from concentration versus time curve showed that the appropriate oral/IV is 1.6 for maintenance GvHD prophylaxis for outpatients could be helpful. Cyclosporine plasma concentration at 0.5 and 6 h after IV administration showed the highest correlation with AUC of this drug.
异基因造血干细胞移植（AHSCT）是治疗多种血液系统疾病和先天性疾病的主要方法。移植物抗宿主病（GvHD）是AHSCT一种危及生命的不良反应。环孢素是预防GvHD最重要且最常用的药物。由于环孢素的药代动力学存在变异性且不可预测，在每个患者群体和临床环境中会产生不同反应，因此关于其最佳给药方法和药物监测仍存在诸多不确定性。在20例AHSCT受者中，于8个不同时间采集频繁血样以进行环孢素定量，测定静脉注射（IV）和口服给药后的药代动力学参数，并相应评估监测参数。药代动力学参数方面，静脉注射时浓度 - 时间曲线下面积（AUC）、清除率和半衰期的均值±标准差估计分别为5492±1596 ng·h/mL、19.44±6.61 L/h和11.8±5.4 h，口服给药时分别为7637.7±2739.8 ng·h/mL、19.42±6.62 L/h和11.16±5.9 h。发现合适的口服与静脉给药剂量比约为1.6。在监测参数中，C h和C显示单点与曲线下总面积之间回归的决定系数最高。对浓度 - 时间曲线得出的药代动力学参数评估表明，对于门诊患者维持GvHD预防，合适的口服/静脉给药比例为1.6可能会有所帮助。静脉注射后0.5小时和6小时的环孢素血浆浓度与该药物的AUC相关性最高。
