Effect of Conversion From Intravenous to Oral Administration on Cyclosporine Exposure in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Background:

Cyclosporine is an immunosuppressant extensively used for the prevention and treatment of graft-vs-host disease (GvHD) in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). Converting the administration route of cyclosporine from intravenous to oral is common in the early period of allo-HSCT. Various factors may have an impact on the conversion ratio of cyclosporine.

Objective:

To evaluate the effect of converting administration route from intravenous to oral on cyclosporine exposure in pediatric allo-HSCT recipients.

Methods:

Children who underwent allo-HSCT and were administered with cyclosporine for the prevention of GvHD were included. The cyclosporine trough concentration (C0), the trough concentration-dose ratio (CDR), and the conversion ratio were evaluated. Meanwhile, factors related to the bioavailability of cyclosporine were also investigated.

Results:

A total of 67 children with 280 concentrations were involved. The conversion ratio used in the study was approximately 1:2, and a significant decrease in cyclosporine CDR (110.5 vs 41.4 mg/kg per μg/L, P < 0.001) was observed. The overall bioavailability of cyclosporine was approximately 35%. Age younger than 3 years old (β = −10.70, 95% CI = −18.45 to −2.96, P = 0.007) and moderately increased transaminases (β = −17.95, 95% CI = −25.42 to −10.48, P < 0.001) had a significant impact on cyclosporine bioavailability.

Conclusions and Relevance:

A conversion ratio of 1:3 was found to be more appropriate for pediatric allo-HSCT recipients when switching cyclosporine from intravenous to oral administration. Children younger than 3 years old or with moderately increased transaminases had significant lower cyclosporine bioavailability. These results can assist in an individualized approach for patients undergoing cyclosporine formulation switching.