title: Use of sublingual tacrolimus in lung transplant recipients.
abstract: BACKGROUND
  In lung transplant recipients (LTRs), tacrolimus is often utilized as a core component of immunosuppressive regimens. Although tacrolimus can be delivered orally or intravenously, oral tacrolimus is associated with fewer adverse effects. Various reports have suggested that sublingual tacrolimus may be used as an alternative to oral tacrolimus; however, information regarding converting between routes is limited. We aimed to identify a dose conversion ratio between oral and sublingual tacrolimus in LTRs.
  
  
  METHODS
  We identified adult LTRs at the University of California, San Francisco, who transitioned between oral and sublingual tacrolimus between 2005 and 2010 (n = 34). For tacrolimus, we obtained steady-state blood concentrations and total daily doses before and after the route conversion. Blood concentrations divided by daily doses were calculated for each route. The conversion ratio was then defined as: (blood concentration(sublingual)/daily dose(sublingual))/(blood concentration(oral)/daily dose(oral)). This ratio was tested in inpatient vs outpatient settings and in the presence of impaired gastric emptying. Adverse effects, including nephrotoxicity, hepatotoxicity and anaphylaxis, were evaluated.
  
  
  RESULTS
  The conversion ratio of sublingual to oral tacrolimus was 0.46 ± 0.20 (mean ± SD). The ratio was not associated with hospital setting (p = 0.82) or with impaired gastric emptying (p = 0.31). When comparing sublingual to oral tacrolimus administration, there were no differences in serum creatinine, liver function tests or anaphylaxis.
  
  
  CONCLUSIONS
  Tacrolimus administered sublingually at approximately half of the oral dose achieves therapeutic blood concentrations and is safe in LTRs. Delivery via the sublingual route using this conversion ratio may aid clinicians in maintaining therapeutic tacrolimus blood concentrations while avoiding the need for intravenous administration.
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, California 94143-0622, USA. katherine.watkins@ucsfmedctr.org
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Watkins
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Boettger
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Hanger
authors.forename: Lorriana E
authors.initials: LE
authors.lastname: Leard
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.forename: Charles W
authors.initials: CW
authors.lastname: Hoopes
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Singer
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus