title: Ocular safety and pharmacokinetics study of FK506 suspension eye drops after corneal transplantation.
abstract: OBJECTIVE
  The aim of this study was to investigate the sensitization, pharmacokinetics, and absorption of FK506 after corneal transplantation.
  
  
  METHODS
  New Zealand albino rabbits were divided into normal and corneal transplantation groups. Each group was divided into 5 subgroups--saline, blank matrix, high-dose, medium-dose, and low-dose, respectively. There were 10 rabbits in each subgroup. One drop (25 μL) of FK506 was administered topically to both eyes of the rabbits 4 times daily for 30 days. Thirty days later, 5 rabbits of each subgroup were sacrificed after the administration of the last dose. Both eyes were enucleated; the left eye was used for pathologic examination and the right eye for the determination of FK506 distribution. The other 5 rabbits in each subgroup were sacrificed 14 days after the former 5 rabbits were sacrificed, and their eyes were enucleated for pathologic examination and tissue distribution determination as the former 5 rabbits in each subgroup (the second batch).
  
  
  RESULTS
  Fluorescein staining and local ocular reaction provided evidence that there were no significant differences between control and FK506-instilled eyes in the rabbit model at any of the tested doses. Histologic examination revealed no ocular abnormality in the rabbits instilled with any doses of FK506 eyedrop. The peak serum concentration (C(max)) of systemic absorption ranged from 4.31±0.79 ng/mL to 14.89±6.85 ng/mL.
  
  
  CONCLUSIONS
  Our study suggests that up to 0.1% FK506 administered 4 times a day (q.i.d.) topically is safe for the rabbit eye. However, further safety studies are required in view of systemic adverse effects.
authors.affiliation: Zhongshan Ophthalmic Center at Sun Yat-sen University, The State Key Laboratory of Ophthalmology, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yuan
authors.forename: Jia-jie
authors.initials: JJ
authors.lastname: Zhai
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.forename: Shi-you
authors.initials: SY
authors.lastname: Zhou
authors.forename: Jia-qi
authors.initials: JQ
authors.lastname: Chen
mesh_terms: D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016039:Corneal Transplantation; D004305:Dose-Response Relationship, Drug; D015353:Eye Enucleation; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D011817:Rabbits; D013535:Suspensions; D016559:Tacrolimus / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D013535:Suspensions; D016559:Tacrolimus