title: Evaluation of the pharmacokinetics and ocular tolerance of a microemulsion containing tacrolimus.
abstract: OBJECTIVE
  Tacrolimus is a potent immunosuppressive agent with limited corneal penetration. Microemulsions can increase the drug solubility and enhance drug absorption in the eye. This work aimed to develop a tacrolimus microemulsion as well as to characterize and to evaluate its ocular tolerance and pharmacokinetics after topical application in rabbits.
  
  
  METHODS
  The microemulsion was prepared by the titration with the cosurfactant technique and its physical-chemical parameters and stability were determined. The cytotoxicity was evaluated using the corneal epithelium and conjunctiva cell lines. The ocular pharmacokinetic parameters in rabbits were determined and compared with that obtained after instillation of tacrolimus suspension.
  
  
  RESULTS
  The microemulsion containing tacrolimus was successfully developed. It was nonirritating to rabbits' eyes and it was also not toxic to the corneal and conjunctival cells. When compared to the suspension, the microemulsion containing tacrolimus presented higher values of AUC (2,912.5±245.4 min.ng/mL vs. 1,669.8±93 min.ng/mL) and Cmax (26.8±2.3 ng/mL vs. 20.7±2.8 ng/mL). On the other hand, the Cl/F value was smaller when compared to the suspension that may decrease the number of applications of eye drops.
  
  
  CONCLUSIONS
  The developed microemulsion could be an alternative to reduce the systemic adverse effects of tacrolimus and, consequently, increase the patient compliance to the treatment.
authors.affiliation: 1 Faculty of Pharmacy, Federal University of Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Armando
authors.initials: A
authors.lastname: Silva-Cunha
authors.forename: Gisele Rodrigues
authors.initials: GR
authors.lastname: da Silva
authors.forename: Whocely Victor
authors.initials: WV
authors.lastname: de Castro
authors.forename: Sílvia Ligório
authors.initials: SL
authors.lastname: Fialho
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D019540:Area Under Curve; D002460:Cell Line; D003228:Conjunctiva / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism*; D004355:Drug Stability; D004655:Emulsions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D010316:Particle Size; D011817:Rabbits; D013535:Suspensions; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D013535:Suspensions; D016559:Tacrolimus