Effect of conversion from intravenous to oral administration on cyclosporine exposure in pediatric allogeneic hematopoietic stem cell transplantation

Aim To evaluate the effect of converting administration route from intravenous to oral on cyclosporine exposure in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods Children underwent allo-HSCT and administered with cyclosporine for the prevention of graft-versus-host disease (GvHD) were included. The cyclosporine trough concentration (C 0 ), the trough concentration-dose ratio (CDR), and the conversion ratio of switching from intravenous to oral administration 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 of switching from intravenous to oral administration 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 and increased transaminases had significantly impact on cyclosporine bioavailability, with coefficient of -10.18 (95% CI: -17.07, -3.29, P =0. 004) and -21.18 (95% CI: -26.72, -15.65, P <0.001), respectively, while gender, conversion date, oral formulation, oral mucositis, diarrhea and concomitant antifungal agents presented no significant impact. Conclusions A conversion ratio of 1:3 was more appropriate for pediatric allo-HSCT recipients when switching cyclosporine from intravenous to oral administration. Children younger than 3 years or with increased transaminases had significantly lower cyclosporine bioavailability. Cyclosporine concentration should be monitored more frequently during the conversion period.