title: Evaluation of the Ocular Tolerance of Three Tacrolimus Topical Pharmaceutical Preparations by Bovine Corneal Opacity and Permeability Test.
abstract: Tacrolimus ocular preparations are commonly employed in autoimmune or inflammatory ocular disorders. However, currently there are not yet approved ocular formulations. Tacrolimus ocular side effects have been reported in clinical use, so the evaluation of different pharmaceutical preparations is mandatory. In this study, the local corneal tolerance and safety profile of three common tacrolimus 0.03% pharmaceutical preparations were evaluated.
  
  
  
  Corneal irritation and permeability of tacrolimus preparations were evaluated with the bovine corneal opacity and permeability (BCOP) test. Complementary corneal hematoxylin/eosin and immunohistochemistry staining for tight junctions and adherent junctions E-cadherin, VE-cadherin and zonula occludens-1 were examined and scored to evaluate and to confirm corneal disruption and irritation scores obtained with the BCOP method.
  
  
  
  Commercial brand ointment (Protopic®), topical compounded eye ointment (pharmacy elaboration) and tacrolimus suspension eye drops (elaborated from parenteral prograf®) were tested as potential ocular preparations to be used in clinics. Tacrolimus preparations hereby studied do not alter the opacity and permeability of the bovine cornea by more than three units, measured by the In Vitro Irritancy Score, neither affected the immunohistochemical parameters, composite score or transepithelial electrical resistance.
  
  
  
  Tacrolimus preparations studied can be safely applied as a topical ocular treatment.
authors.affiliation: a Research Foundation of General Hospital of Valencia , Valencia , Spain.|b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pastor-Clerigues
authors.affiliation: a Research Foundation of General Hospital of Valencia , Valencia , Spain.|c CIBERES , Health Institute Carlos III , Valencia , Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Serrano
authors.affiliation: a Research Foundation of General Hospital of Valencia , Valencia , Spain.|b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.|c CIBERES , Health Institute Carlos III , Valencia , Spain.|d Clinical Research Unit (UIC) , University General Hospital Consortium , Valencia , Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Milara
authors.affiliation: a Research Foundation of General Hospital of Valencia , Valencia , Spain.|b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Marti-Bonmati
authors.affiliation: b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Lopez-Perez
authors.affiliation: b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Garcia-Montanes
authors.affiliation: b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Sanfeliu
authors.affiliation: b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Saval-Victoria
authors.affiliation: a Research Foundation of General Hospital of Valencia , Valencia , Spain.|b Hospital Pharmacy , University General Hospital Consortium , Valencia , Spain.|c CIBERES , Health Institute Carlos III , Valencia , Spain.|d Clinical Research Unit (UIC) , University General Hospital Consortium , Valencia , Spain.|e Department of Pharmacology , Faculty of Medicine, University of Valencia , Valencia , Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
mesh_terms: D000818:Animals; D002417:Cattle; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003318:Corneal Opacity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007509:Irritants / Q000633:toxicity; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D007509:Irritants; D009883:Ophthalmic Solutions; D016559:Tacrolimus
keywords: BCOP; corneal permeability; eye drops; eye irritation; tacrolimus