Variable magnitude of drug interaction between oral voriconazole and cyclosporine A in recipients of allogeneic hematopoietic stem cell transplantation.

Drug interaction between voriconazole and calcineurin inhibitors is often problematic after allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. We previously demonstrated an unpredictable inter-individual variability in the magnitude of this drug interaction; however, the route of drug administration was not taken into account. In this study, the drug interaction between voriconazole and calcineurin inhibitors was further analyzed under the condition that both agents were administered orally. Twenty adult recipients of HSCT who had already been on a steady dose of oral cyclosporine A (CsA) and were started on oral voriconazole (400 mg/d) were eligible. The changes in the concentration/dose (C/D) ratio of CsA were evaluated by comparing the trough concentrations of CsA measured before and 7-10 d after initiating voriconazole. The median C/D ratio of CsA increased significantly from 64.1 to 114.3 (ng/mL)/(mg/kg) after initiating voriconazole (p < 0.01), and the median increase was 83.0% (range, 0.3-224.7%). The plasma concentration of voriconazole did not correlate significantly with the increase of the C/D ratio (ρ = -0.18, p = 0.45). These results indicate that the magnitude of drug interaction between oral voriconazole and CsA is widely variable, and it could not be explained by the difference in the blood levels of voriconazole. Further studies are required to elucidate the mechanism for this variability.