[Transcorneal-paracorneal penetration route for topical application of drugs to the eyt. Mycophenolate mofetil as a model substance].
OBJECTIVE
Topically applied drugs can penetrate transcorneally or paracorneally (transsclerally). There are only few studies to demonstrate the relationship of both penetration routes. The immuno-modulator mycophenolate mofetil (MMF), ester and pro-drug of mycophenolic acid (MPA), is a promising substance for such studies.


METHODS
Rabbit eyes were treated with different preparations of MMF as a cyclodextrin complex (MM-CD) and as a suspension (MMF-SP) and MPA as a cyclodextrin complex (MPA-CD). The concentrations of both compounds were measured in the cornea, conjunctiva, aqueous humor, vitreous body and iris-ciliary body.


RESULTS
Only MPA is detectable in the cornea after application of MMF-CD and MMF-SP. In the aqueous humor high concentrations of MPA are detectable after 60 min. In the iris-ciliary body both MMF and MPA can be found.


CONCLUSIONS
The intraocularly detected mycophenolate mofetil represents the paracorneally penetrated fraction. After topical application of mycophenolate mofetil in suitable preparations high concentrations of the active substance can be achieved intraocularly. These favourable pharmacokinetic characteristics are promising for new therapeutic strategies in immune-mediated diseases of the anterior part of the eye.
D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000378:metabolism; D003505:Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics; D005123:Eye / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution
D003505:Cyclodextrins; D007166:Immunosuppressive Agents; D011355:Prodrugs; D009173:Mycophenolic Acid