Evaluation of Cyclosporine Pharmacokinetic, Monitoring, and Dosing Parameters for GVHD Prophylaxis in Hematopoietic Stem Cell Transplant (HSCT) Recipients
Allogeneic hematopoietic stem cell transplantation (AHSCT) is a major method of treatmentfor different hematologic and congenital disease. Graft versus host disease (GvHD) is a lifethreateningadverse effect of AHSCT. Cyclosporine is the most important and common agentfor GvHD prophylaxis. Because of variable and unpredictable pharmacokinetics of cyclosporinethat produces different responses in each patients group and clinical setting, there are still lots ofuncertainties about its optimal method of administration and monitoring of this drug. Frequentblood samples in eight different times were taken for cyclosporine quantification in twentyAHSCT recipients and pharmacokinetic parameters determined in both intravenous (IV) and oraladministration and monitoring parameters assessed accordingly. Of pharmacokinetic parametersmean ± SD area under concentration – time curve (AUC), clearance, and half-life were estimatedto 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 tointravenous dosing ratio found to be about 1.6. Of monitoring parameters, C0.5 h and C6 showedthe highest coefficient of determination for regression between single points and total area undercurve. Evaluation of pharmacokinetic parameters derived from concentration versus time curveshowed that the appropriate oral/IV is 1.6 for maintenance GvHD prophylaxis for outpatientscould be helpful. Cyclosporine plasma concentration at 0.5 and 6 h after IV administrationshowed the highest correlation with AUC of this drug.
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