title: Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole.
abstract: OBJECTIVE
  Although the drug interaction between fluconazole and calcineurin inhibitors has been established, the influence of the route of fluconazole administration on its drug interaction with calcineurin inhibitors has yet to be fully examined. The aim of the present study is to examine whether different routes of fluconazole administration alter its drug interactions with intravenous calcineurin inhibitors.
  
  
  METHODS
  In 53 recipients of allogeneic hematopoietic cell transplantation receiving calcineurin inhibitors intravenously, steady-state whole-blood levels of cyclosporine A (CsA) or tacrolimus were measured after the route of fluconazole (200 mg/day) administration was switched from intravenous to oral.
  
  
  RESULTS
  The mean steady-state whole-blood level of CsA or tacrolimus significantly increased after the route of fluconazole administration was switched from intravenous to oral (CsA: to 394 +/- 28.4 from 362 +/- 17.8 ng/mL; tacrolimus: to 18.8 +/- 0.64 from 17.4 +/- 0.39 ng/mL, P < 0.05).
  
  
  CONCLUSIONS
  This finding strongly suggests that oral fluconazole has a greater impact on its drug interactions with intravenous calcineurin inhibitors than intravenous fluconazole. Monitoring of blood levels of intravenous calcineurin inhibitors is recommended when the route of fluconazole administration is switched from intravenous to oral.
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Mihara
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Aisa
authors.forename: Rie
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Iketani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000493:pharmacokinetics; D004347:Drug Interactions; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D012189:Retrospective Studies; D016559:Tacrolimus / Q000493:pharmacokinetics
chemical_list: D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015725:Fluconazole; D016559:Tacrolimus