Influence of topical cyclosporine A and dissolvent on corneal epithelium permeability of fluorescein.
The corneal stroma is the major barrier to penetration for the lipophilic Cyclosporine A (CsA) molecule and prevents the use of the common ophthalmic solvents. At present, corn oil, castor oil and olive oil are the three most commonly used vehicles. The aim of this study was to determine the effect that topically applied CsA dissolved in different oils has on corneal epithelial permeability measured by fluorophotometry. Forty healthy volunteers, with absence of ocular or systemic disease and not receiving topical or systemic drugs were enrolled. Measurements were taken before and 45 min after the instillation of 40 microliters of a 2% aqueous solution of sodium fluorescein without preservatives. Basal corneal permeability and the permeability 24 h after the instillation of 2% CsA-olive oil, olive oil alone, 2% CsA-castor oil, castor oil alone, 2% CsA-corn oil and corn oil alone, were calculated. To prepare the topical 2% CsA, a Sandimmun oral solution (Sandoz, Basel, Switzerland) was employed under sterile conditions. We found that epithelial permeability 24 h after the instillation of any CsA formulations or solvents increased more than 6.62 times (p <0.001). No differences in corneal permeability values were found between any of the CsA formulations and the vehicles. We conclude that oils used to dissolve CsA are mainly responsible for the increased corneal epithelial permeability. No differences were found in the effects of the tested solvents on corneal epithelial permeability.
Benítez del Castillo
J M
JM
Instituto de Investigaciones Oftalmologicas Ramon Castroviejo, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Castillo
A
A
Toledano
N
N
Durán
S
S
del Aguila
C
C
Otero
M
M
García-Sanchez
J
J
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019793:Fluorescein; D005452:Fluoresceins / Q000493:pharmacokinetics*; D015590:Fluorophotometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009821:Oils / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000493:pharmacokinetics; D012016:Reference Values
D005452:Fluoresceins; D007166:Immunosuppressive Agents; D009821:Oils; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D016572:Cyclosporine; D019793:Fluorescein