title: Micafungin does not influence the concentration of tacrolimus in patients after allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Tacrolimus is commonly used in stem cell transplant recipients for prophylaxis of graft-vs-host disease. Micafungin is widely used as a strong antifungal agent in empirical therapy in patients with febrile neutropenia. Both tacrolimus and micafungin are substrates of cytochrome P450 3A4 in vitro. Therefore, there is risk of drug interaction with concomitant administration of these drugs.
  
  
  OBJECTIVE
  To estimate the drug interaction of tacrolimus and micafungin by evaluating the pharmacokinetics in 6 patients who had undergone allogeneic stem cell transplantation.
  
  
  RESULTS
  The mean (SD) concentration-dose ratio of tacrolimus in all patients at 1, 4, 8, and 24 hours after concomitant administration of micafungin was 607 ± 306, 653 ± 328, 699 ± 340 and 671 ± 403 (ng/mL)/(mg/kg/d), respectively, and without micafungin was 756 ± 314 (ng/mL)/(mg/kg/d). The percentage of the concentration-dose ratio in patients treated with tacrolimus and micafungin vs patients treated with tacrolimus alone was 98%, 105%, 112%, and 108% at 1, 4, 8, and 24 hours, respectively. For both tacrolimus and micafungin, the 90% confidence intervals for the primary pharmacokinetic parameters (ie, the concentration-dose ratio at each point) ranged from 80% to 125%.
  
  
  CONCLUSIONS
  We conclude that there is no drug interaction between tacrolimus and concomitantly administered micafungin in stem cell transplantation recipients.
authors.affiliation: Department of Pharmacy, Kagawa University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Fukuoka
authors.forename: O
authors.initials: O
authors.lastname: Imataki
authors.forename: H
authors.initials: H
authors.lastname: Ohnishi
authors.forename: A
authors.initials: A
authors.lastname: Kitanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D019337:Hematologic Neoplasms / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D055666:Lipopeptides / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D012008:Recurrence; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D000077551:Micafungin; D016559:Tacrolimus