title: Drug interaction between oral solution itraconazole and calcineurin inhibitors in allogeneic hematopoietic stem cell transplantation recipients: an association with bioavailability of oral solution itraconazole.
abstract: To assess the drug interaction between oral solution itraconazole and calcineurin inhibitors, 10 recipients of allogeneic hematopoietic stem cell transplantation (HSCT), in whom oral solution itraconazole was started when they had been on a steady dose of calcineurin inhibitors (cyclosporine A or tacrolimus), were retrospectively evaluated. The concentration/dose [C/D; (ng/mL)/(mg/kg)] ratio of calcineurin inhibitors significantly increased after initiating oral solution itraconazole, and the increase at 7-10 days after initiating itraconazole was 93.7%, ranging from 37.3 to 328.2%. The plasma level of itraconazole/hydroxyitraconazole was significantly correlated with the increase in the C/D ratio of calcineurin inhibitors (correlation coefficient, 0.65; P < 0.05). These results suggest that oral solution itraconazole significantly interacts with calcineurin inhibitors with a wide interindividual variability in allogeneic HSCT recipients, which could partly be explained by the variable bioavailability of oral solution itraconazole.
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan. tmori@sc.itc.keio.ac.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Aisa
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D000284:Administration, Oral; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019703:Calcineurin / Q000493:pharmacokinetics; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014184:Transplantation, Homologous
chemical_list: D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D017964:Itraconazole; D016572:Cyclosporine; D019703:Calcineurin; D016559:Tacrolimus