Intraocular Penetration Kinetics of Prednisolone after Subconjunctival Injection in Rabbits

Abstract

Prednisolone concentrations in cornea, aqueous humor, and vitreous humor and the residual amount in conjunctival tissue were assayed by high-performance liquid chromatography during a 14-hour period after subconjunctival injection of prednisolone sodium succinate in rabbits. Prednisolone was concentrated in the corneal epithelium and reached a peak within 5 min, whereas the peak level of prednisolone in stroma-endothelium was achieved 1 h after the injection. There was an apparent linear binding of prednisolone with the ocular tissue homogenates and fluids except for the vitreous humor. However, the protein binding of prednisolone with vitreous humor showed marked concentration dependency. A pharmacokinetic model involving a rapid conversion to prednisolone from its ester prodrug, first-order transfer to various tissues, and first-order elimination of unbound prednisolone from vitreous humor succeeded in predicting the observed concentration-time profiles of prednisolone in various ocular tissues and fluids after subconjunctival injection at three different doses: 0.1, 1.0, and 10.0 mg/kg. The present model predicted that absorption into precorneal area and epithelium and direct penetration into aqueous humor and vitreous humor are 1.7, 0.1, and 0.2% of the applied dose, respectively, and that almost the entire dose (98%) is absorbed into the systemic circulation, with a half-life of 38 min.

Transscleral Coulomb-controlled Iontophoresis of Methylprednisolone into the Rabbit Eye: Influence of Duration of Treatment, Current Intensity and Drug Concentration on Ocular Tissue and Fluid Levels

“…However, higher concentrations of prednisolone were achieved in the cornea, the aqueous humor and to a lesser extent in the vitreous compared with concentrations achieved after i.v. administration of equivalent amounts of drug (Tsuji et al, 1988). Similar results have been found with peribulbar injection compared with systemic oral administration of prednisone (Weijtens et al, 1997(Weijtens et al, , 1998.…”

“…) was injected as previously described (Tsuji, Tamai and Sasaki 1988). The HMP powder, in sterile injectable water, is an anionic neutral solution (pH 7).…”

“…The HMP powder, in sterile injectable water, is an anionic neutral solution (pH 7). In the rabbit eye tissues, HMP is rapidly hydrolyzed to methylprednisolone (MP) (Tsuji, Tamai andSasaki 1987, 1988). Therefore the levels of MP were measured by high pressure liquid chromatography (HPLC) technique (Lawson, 1985) as an indication of HMP penetration in the ocular tissues.…”

Optimization of Subconjunctival Biodegradable Microfilms for Sustained Drug Delivery to the Anterior Segment in a Small Animal Model

“…For example, it has been reported that the half-life of prednisolone after subconjunctival injection is only 38 minutes. 12 Surodex (Oculex Pharmaceuticals, Inc., Sunnyvale, CA), a dexamethasone anterior segment drug delivery system, has been proven to be effective to treat inflammation after cataract surgery. 13 Even though satisfactory anti-inflammatory results were achieved, adverse side effects, such as implant migration in anterior chamber or peripheral anterior synechiae, have been reported.…”

Subconjunctival betamethasone is of benefit after cataract surgery

“…19 High concentrations of steroid in the anterior chamber can be achieved by this route. 20,21 Topical steroid, if given frequently, has been shown to be more effective than a single subconjunctival injection at suppressing corneal inflammation in rabbits.18 However, most surgeons cover the operated eye for 16-24 hours fol lowing cataract surgery, and frequent instillation of drops is therefore not feasible. In this situation, a subconjunctival injection given at the end of surgery, during the period of anaesthesia, provides a practical and painless means of maintaining steroid cover during the early post-operative phase when intraocular inflammation becomes active.…”