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

Document Type: Research article

Authors

1 Student’ Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Bone Marrow Transplant, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 lifethreatening
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.

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