Evaluation of Cyclosporine Pharmacokinetic, Monitoring, and Dosing Parameters for GVHD Prophylaxis in Hematopoietic Stem Cell Transplant (HSCT) Recipients.

Abstract

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, C0.5 h and C6 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.