The effects of oral and topical corticosteroid in rabbit corneas.
BACKGROUND
To determine the most effective route of administration of corticosteroids in the treatment of ocular surface disease, by characterizing the difference between oral prednisolone and topical dexamethasone administration using an animal model.


METHODS
Pharmacokinetic analyses determined the corticosteroid concentrations in the normal ocular tissues of rabbits after oral or topical administration of corticosteroids using LC-MS/MS. In wound healing analyses, the area of the epithelial defect created by keratectomy using a 6-mm trephine was calculated with an image analyzer using an orally or topically steroid-administrated animal model. The average size of basal epithelial cells, the frequency of mitotic basal epithelial cells, the number of squamous cells, and the number of hypertrophic stromal fibroblasts were determined in the enucleated corneal tissues after wound closure.


RESULTS
By slit lamp examination, no remarkable differences were observed between orally and topically administered groups. Pharmacokinetic analyses showed that the distribution of dexamethasone after topical administration was superior to that after oral administration in the cornea. In contrast, both concentrations of corticosteroid applied topically and orally were similar with regards to AUCs (area under the concentration-time curve) in the conjunctiva. Although the healing rate was slower in the topical group, all corneas were almost healed within 96 h in the wound healing analysis. According to the histological analyses of epithelial cells, the average basal cell size was larger, the frequency of mitotic basal cells was greater, and the number of squamous epithelial cell layers was lower in the topically administered group although all of these differences were with no statistical significance. However, the number of hypertrophic stromal fibroblasts in the topically administered group was significantly lower than that in the orally administered group.


CONCLUSIONS
There are different distributions and effects between orally and topically administered corticosteroids on the ocular surface. The data may provide the useful information in selecting the appropriate route of corticosteroid application for the treatment of ocular surface disease.
Department of Ophthalmology, Japan Community Health Care Organization, Hoshigaoka Medical Center, 4-8-1, Hoshigaoka, Hirakata city, Osaka, 5738511, Japan. sasakis@sa2.so-net.ne.jp.
Kaoru
K
Araki-Sasaki
Research and Development Division, Santen Pharmaceutical Co., Ltd., 8916-16, Takayama-cho, Ikoma city, Nara, 6300101, Japan.
Osamu
O
Katsuta
Research and Development Division, Santen Pharmaceutical Co., Ltd., 8916-16, Takayama-cho, Ikoma city, Nara, 6300101, Japan.
Hidetoshi
H
Mano
Research and Development Division, Santen Pharmaceutical Co., Ltd., 8916-16, Takayama-cho, Ikoma city, Nara, 6300101, Japan.
Takashi
T
Nagano
Research and Development Division, Santen Pharmaceutical Co., Ltd., 8916-16, Takayama-cho, Ikoma city, Nara, 6300101, Japan.
Masatsugu
M
Nakamura
D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D065306:Corneal Injuries / Q000188:drug therapy / Q000473:pathology; D003319:Corneal Stroma / Q000166:cytology / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D053719:Tandem Mass Spectrometry; D014945:Wound Healing / Q000187:drug effects
D005938:Glucocorticoids; D003907:Dexamethasone; D011239:Prednisolone
Cornea; Corticosteroid; Keratitis; Pharmacokinetics; Wound healing