title: Sublingual tacrolimus: a pharmacokinetic evaluation pilot study.
abstract: OBJECTIVE
  To evaluate and compare the pharmacokinetic parameters of sublingual and oral tacrolimus in the presence and absence of a drug that interacts with tacrolimus at the intestinal level.
  
  
  METHODS
  Prospective, randomized, open-label, parallel-group pilot study.
  
  
  METHODS
  Large, urban, academic medical center.
  
  
  METHODS
  Six adults with end-stage renal disease who were awaiting kidney transplantation; five completed the study.
  
  
  METHODS
  Patients were randomized in a 1:1 ratio to receive tacrolimus plus a clotrimazole troche (a drug that interacts with tacrolimus at the intestinal level) or tacrolimus plus nystatin suspension. For the tacrolimus route of administration, patients first received sublingual tacrolimus for five doses; after a 2-day washout period, they received oral tacrolimus for five doses.
  
  
  RESULTS
  Demographic characteristics, concomitant medications, tacrolimus dosing information, and steady-state venous whole blood specimen values after tacrolimus administration were collected. Noncompartmental pharmacokinetics were calculated from the tacrolimus blood concentrations in samples collected at multiple time points after drug administration. The area under the concentration-time curve from 0-6 hours for sublingual and oral tacrolimus ranged from 27.2-66 and 32.4-76 mg·hour/L, respectively, in the tacrolimus plus clotrimazole group and from 9.3-63 and 4.9-23.2 mg·hour/L, respectively, in the tacrolimus plus nystatin group. The average maximum concentration was higher during sublingual administration than during oral administration: 16.7 versus 12.9 ng/ml in the tacrolimus plus clotrimazole group and 9.5 versus 6 ng/ml in the tacrolimus plus nystatin group.
  
  
  CONCLUSIONS
  An oral-to-sublingual tacrolimus dose conversion should be evaluated on an individual basis. A 1:1 dose conversion may be appropriate in the presence of clotrimazole, whereas a 2:1 oral-to-sublingual conversion may be appropriate when there are no concomitantly interacting drugs. These findings should be investigated further in pharmacokinetic studies conducted in solid organ transplant recipients.
authors: NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, New York 10032, USA. det9021@nyp.org
authors: Demetra
authors: D
authors: Tsapepas
authors: Stuart
authors: S
authors: Saal
authors: Steven
authors: S
authors: Benkert
authors: Daniel
authors: D
authors: Levine
authors: Merdie
authors: M
authors: Delfin
authors: Serge
authors: S
authors: Cremers
authors: Shawn
authors: S
authors: Amann
authors: Darshana
authors: D
authors: Dadhania
authors: Sandip
authors: S
authors: Kapur
authors: Meredith
authors: M
authors: Aull
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus