Oral Administration of Stereoisomeric Prednisolone Prodrugs in Rats - Abstract
Prednisolone is commonly indicated for the treatment of ocular allergy, inflammation and uveitis. Topical administration of prednisolone suffers several limitations, which include poor aqueous solubility, rapid tear turnover rate, high cellular efflux and drainage to systemic circulation. Moreover, prednisolone permeation to posterior tissues such as retina following topical administration is highly restricted by aqueous humor outflow. The primary objective of the present study is to determine oral
absorption of Stereoisomeric prodrugs of prednisolone. In vitro permeability of LLP, LDP, DLP, DDP across Caco2 cells was found to be 1.8, 2.3, 2.1, 1.2 fold higher than prednislone. The Km of LLP, LDP, DLP towards rat liver microsome was 3.1, 3.1, 4.9
fold higher than prednisolone, which demonstrates lower affinity. To substantiate in vitro results, oral absorption study of prodrugs was conducted in rats. Results obtained from these studies indicate that Stereoisomeric prodrugs may be a viable strategy to improve ocular drug absorption following oral administration.