title: Dose increase needed in most cystic fibrosis lung transplantation patients when changing from twice- to once-daily tacrolimus oral administration.
abstract: OBJECTIVE
  The aim of this pharmacokinetic (PK) study was to evaluate tacrolimus (TAC) exposure in stable cystic fibrosis (CF) lung transplant (LT) recipients, converted from TAC twice daily to TAC once daily in an open-label, prospective, single-centre study.
  
  
  METHODS
  Eligible patients were post-transplant CF patients (18-65 years) with stable lung function, on stable doses of TAC twice daily and who were candidates to switch to TAC once daily. Twelve consecutive patients were included in the study. Patients had their first PK analysis on day 1, still under the stable TAC twice-daily regimen, and were converted to TAC once daily from day 2 onwards. The doses were adjusted according to clinical judgement to achieve target levels, and a second 24-h PK period profile was obtained once the patient was on a stable dosage on the therapeutic range.
  
  
  RESULTS
  The mean total (SD) daily dose of TAC twice daily at baseline upon enrolment was 0.17 (0.10) mg/kg/day. The mean (SD) daily dose of TAC once daily after adjustments was 0.22 (0.12) mg/kg/day. In order to achieve target C min levels with a similar AUC0-24, 82% of subjects who were converted to TAC once daily required an increase of dose, in a range of 0-66.7%, with a mean dose increase of 28%.
  
  
  CONCLUSIONS
  Our study results indicate that the switch for conversion from TAC twice daily to TAC once daily in patients with CF may need dose adjustment in order to reach levels within the therapeutic target.
authors.affiliation: Clinical Pharmacology Department, Puerta de Hierro-Majadahonda University Hospital, Calle Manuel de Falla, 1, 28222, Majadahonda, Spain.
authors.forename: Gustavo Adolfo Centeno
authors.initials: GAC
authors.lastname: Soto
authors.affiliation: Clinical Pharmacology Department, Puerta de Hierro-Majadahonda University Hospital, Calle Manuel de Falla, 1, 28222, Majadahonda, Spain. mariabelen.ruiz@salud.madrid.org.
authors.forename: Belén
authors.initials: B
authors.lastname: Ruiz-Antorán
authors.affiliation: Pneumology Department, Puerta de Hierro-Majadahonda University Hospital, Madrid, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Laporta
authors.affiliation: Clinical Pharmacology Department, Puerta de Hierro-Majadahonda University Hospital, Calle Manuel de Falla, 1, 28222, Majadahonda, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Sancho
authors.affiliation: Pneumology Department, Puerta de Hierro-Majadahonda University Hospital, Madrid, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Lázaro
authors.affiliation: Clinical Pharmacology Department, Puerta de Hierro-Majadahonda University Hospital, Calle Manuel de Falla, 1, 28222, Majadahonda, Spain.
authors.forename: Concepción Payares
authors.initials: CP
authors.lastname: Herrera
authors.affiliation: Clinical Pharmacology Department, Puerta de Hierro-Majadahonda University Hospital, Calle Manuel de Falla, 1, 28222, Majadahonda, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Salcedo
authors.affiliation: Clinical Pharmacology Unit, Marques de Valdecilla Hospital, Santander, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Cos
authors.affiliation: Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clinic Barcelona; Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ferrán
authors.initials: F
authors.lastname: Torres
authors.affiliation: Pneumology Department, Puerta de Hierro-Majadahonda University Hospital, Madrid, Spain.
authors.forename: Piedad
authors.initials: P
authors.lastname: Usetti
authors.affiliation: Clinical Pharmacology Department, Puerta de Hierro-Majadahonda University Hospital, Calle Manuel de Falla, 1, 28222, Majadahonda, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Avendaño-Sola
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016040:Lung Transplantation / Q000379:methods; D008297:Male; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus