Topically Applied Steroids in Corneal Disease

Tear Film Pharmacokinetics and Systemic Absorption Following Topical Administration of 1% Prednisolone Acetate Ophthalmic Suspension in Dogs

“…However, further assessment showed that the average tear film concentration (C avg ) and the overall drug exposure (AUC last ) were both significantly higher (by 39%) in eyes receiving two vs. one drop of 1% prednisolone acetate. This finding contrasts with topical instillation of 1% fluorescein solution in dogs (8), and could be partly explained by a larger amount of drug particles being sequestered in the conjunctival cul-de-sac (15,16) when two drops of an ophthalmic suspension are applied to the ocular surface. Further studies are needed to verify this hypothesis and determine whether this "statistically significant" finding is at all significant from a clinical perspective (i.e., therapeutic benefit, toxicity).…”

“…Given the relatively short precorneal retention time of prednisolone suspension, other strategies could be considered to optimize the therapeutic efficacy of topical corticosteroids: (i) Increase the concentration of the formulation-a 1% preparation of prednisolone acetate produced higher drug concentrations in the eye (cornea, conjunctiva, aqueous humor) compared to 0.125 and 0.5% preparations (6,15); however, 1% is the highest concentration that is commercially available, and further increases in concentration did not augment the therapeutic response in one study of inflammatory keratitis (27); (ii) Increase the viscosity of the formulation-drug concentrations in ocular tissues were higher when prednisolone was coupled with highly viscous polymers such as carboxypolymethylene (28) or carbomer 0.5% (6); (iii) Increase the frequency of administration-reduction in inflammatory cells invading the cornea was significantly better when prednisolone acetate was applied at 1 h compared to 4 h intervals, and was further improved when the drug was applied at 15 min intervals (29); (iv) Consider an alternate corticosteroid-for instance, 0.05% difluprednate administered at a lower frequency than 1% prednisolone acetate is at least as effective in controlling inflammation associated with paracentesis-induced uveitis in dogs (30) or endogenous uveitis in humans (31).…”

“…In each dog, one eye was chosen at random (Excel software) to receive 35 µL (one drop) of 1% prednisolone acetate ophthalmic suspension (Sandoz Inc., Princeton, NJ, United States), while the other eye received 70 µL (two drops), and this selection was kept constant throughout the study. The experiment extended over 13 consecutive days, with topical prednisolone acetate delivered with a pipette at 8:00 a.m. (each day) and tear fluid collected with dye-free Schirmer strips at the following time points (one collection per day): 0 min (i.e., immediately after instillation and blinking), 1,3,5,15,30,45,60,90,120,240,480, and 720 min. At completion of tear collection each day, both eyes were thoroughly rinsed with eyewash (Eye Wash, OcuSOFT Inc., Richmond, TX, United States) to avoid any carryover of prednisolone acetate from 1 day to another.…”

Tear Film Pharmacokinetics and Systemic Absorption Following Topical Administration of 1% Prednisolone Acetate Ophthalmic Suspension in Dogs

“…However, further assessment showed that the average tear film concentration (C avg ) and the overall drug exposure (AUC last ) were both significantly higher (by 39%) in eyes receiving two vs. one drop of 1% prednisolone acetate. This finding contrasts with topical instillation of 1% fluorescein solution in dogs (8), and could be partly explained by a larger amount of drug particles being sequestered in the conjunctival cul-de-sac (15,16) when two drops of an ophthalmic suspension are applied to the ocular surface. Further studies are needed to verify this hypothesis and determine whether this "statistically significant" finding is at all significant from a clinical perspective (i.e., therapeutic benefit, toxicity).…”

“…Given the relatively short precorneal retention time of prednisolone suspension, other strategies could be considered to optimize the therapeutic efficacy of topical corticosteroids: (i) Increase the concentration of the formulation-a 1% preparation of prednisolone acetate produced higher drug concentrations in the eye (cornea, conjunctiva, aqueous humor) compared to 0.125 and 0.5% preparations (6,15); however, 1% is the highest concentration that is commercially available, and further increases in concentration did not augment the therapeutic response in one study of inflammatory keratitis (27); (ii) Increase the viscosity of the formulation-drug concentrations in ocular tissues were higher when prednisolone was coupled with highly viscous polymers such as carboxypolymethylene (28) or carbomer 0.5% (6); (iii) Increase the frequency of administration-reduction in inflammatory cells invading the cornea was significantly better when prednisolone acetate was applied at 1 h compared to 4 h intervals, and was further improved when the drug was applied at 15 min intervals (29); (iv) Consider an alternate corticosteroid-for instance, 0.05% difluprednate administered at a lower frequency than 1% prednisolone acetate is at least as effective in controlling inflammation associated with paracentesis-induced uveitis in dogs (30) or endogenous uveitis in humans (31).…”

“…In each dog, one eye was chosen at random (Excel software) to receive 35 µL (one drop) of 1% prednisolone acetate ophthalmic suspension (Sandoz Inc., Princeton, NJ, United States), while the other eye received 70 µL (two drops), and this selection was kept constant throughout the study. The experiment extended over 13 consecutive days, with topical prednisolone acetate delivered with a pipette at 8:00 a.m. (each day) and tear fluid collected with dye-free Schirmer strips at the following time points (one collection per day): 0 min (i.e., immediately after instillation and blinking), 1,3,5,15,30,45,60,90,120,240,480, and 720 min. At completion of tear collection each day, both eyes were thoroughly rinsed with eyewash (Eye Wash, OcuSOFT Inc., Richmond, TX, United States) to avoid any carryover of prednisolone acetate from 1 day to another.…”

Molecular Expression and Functional Evidence of a Drug Efflux Pump (BCRP) in Human Corneal Epithelial Cells

“…2 Many topically instilled drugs reach the internal segments of the eye through the cornea. 2 As stated by Dey et al (2003), 2 “these drugs include steroids, 31,32 ß-blockers, 33,34 antibiotics, 35,36,37 and nonsteroidal anti-inflammatory agents. 38 ” The cul-de-sac, as a route for topical drug administration, is the most common route of ocular drug delivery.…”

Vehicle Effects on Ocular Drug Bioavailability I: Evaluation of Fluorometholone

“…It does not seem unreasonable to expect that a highly lipophilic steroid such as fluorometholone will tend to concentrate in the epithelial layer, perhaps even reaching a saturation concentration prior to passage through the hydrophilic layers of the cornea. Such a mechanism is not unlikely and was recently speculated upon for other steroidal compounds in a study using prednisolone acetate (9). In such a process, the rate and extent to which the epi-Vol.…”

Tear Film Pharmacokinetics and Systemic Absorption Following Topical Administration of 1% Prednisolone Acetate Ophthalmic Suspension in Dogs

“…However, further assessment showed that the average tear film concentration (C avg ) and the overall drug exposure (AUC last ) were both significantly higher (by 39%) in eyes receiving two vs. one drop of 1% prednisolone acetate. This finding contrasts with topical instillation of 1% fluorescein solution in dogs (8), and could be partly explained by a larger amount of drug particles being sequestered in the conjunctival cul-de-sac (15,16) when two drops of an ophthalmic suspension are applied to the ocular surface. Further studies are needed to verify this hypothesis and determine whether this "statistically significant" finding is at all significant from a clinical perspective (i.e., therapeutic benefit, toxicity).…”

“…Given the relatively short precorneal retention time of prednisolone suspension, other strategies could be considered to optimize the therapeutic efficacy of topical corticosteroids: (i) Increase the concentration of the formulation-a 1% preparation of prednisolone acetate produced higher drug concentrations in the eye (cornea, conjunctiva, aqueous humor) compared to 0.125 and 0.5% preparations (6,15); however, 1% is the highest concentration that is commercially available, and further increases in concentration did not augment the therapeutic response in one study of inflammatory keratitis (27); (ii) Increase the viscosity of the formulation-drug concentrations in ocular tissues were higher when prednisolone was coupled with highly viscous polymers such as carboxypolymethylene (28) or carbomer 0.5% (6); (iii) Increase the frequency of administration-reduction in inflammatory cells invading the cornea was significantly better when prednisolone acetate was applied at 1 h compared to 4 h intervals, and was further improved when the drug was applied at 15 min intervals (29); (iv) Consider an alternate corticosteroid-for instance, 0.05% difluprednate administered at a lower frequency than 1% prednisolone acetate is at least as effective in controlling inflammation associated with paracentesis-induced uveitis in dogs (30) or endogenous uveitis in humans (31).…”

“…In each dog, one eye was chosen at random (Excel software) to receive 35 µL (one drop) of 1% prednisolone acetate ophthalmic suspension (Sandoz Inc., Princeton, NJ, United States), while the other eye received 70 µL (two drops), and this selection was kept constant throughout the study. The experiment extended over 13 consecutive days, with topical prednisolone acetate delivered with a pipette at 8:00 a.m. (each day) and tear fluid collected with dye-free Schirmer strips at the following time points (one collection per day): 0 min (i.e., immediately after instillation and blinking), 1,3,5,15,30,45,60,90,120,240,480, and 720 min. At completion of tear collection each day, both eyes were thoroughly rinsed with eyewash (Eye Wash, OcuSOFT Inc., Richmond, TX, United States) to avoid any carryover of prednisolone acetate from 1 day to another.…”

Molecular Expression and Functional Evidence of a Drug Efflux Pump (BCRP) in Human Corneal Epithelial Cells

“…2 Many topically instilled drugs reach the internal segments of the eye through the cornea. 2 As stated by Dey et al (2003), 2 “these drugs include steroids, 31,32 ß-blockers, 33,34 antibiotics, 35,36,37 and nonsteroidal anti-inflammatory agents. 38 ” The cul-de-sac, as a route for topical drug administration, is the most common route of ocular drug delivery.…”

Vehicle Effects on Ocular Drug Bioavailability I: Evaluation of Fluorometholone

“…It does not seem unreasonable to expect that a highly lipophilic steroid such as fluorometholone will tend to concentrate in the epithelial layer, perhaps even reaching a saturation concentration prior to passage through the hydrophilic layers of the cornea. Such a mechanism is not unlikely and was recently speculated upon for other steroidal compounds in a study using prednisolone acetate (9). In such a process, the rate and extent to which the epi-Vol.…”

Tear Film Pharmacokinetics and Systemic Absorption Following Topical Administration of 1% Prednisolone Acetate Ophthalmic Suspension in Dogs

“…However, further assessment showed that the average tear film concentration (C avg ) and the overall drug exposure (AUC last ) were both significantly higher (by 39%) in eyes receiving two vs. one drop of 1% prednisolone acetate. This finding contrasts with topical instillation of 1% fluorescein solution in dogs (8), and could be partly explained by a larger amount of drug particles being sequestered in the conjunctival cul-de-sac (15,16) when two drops of an ophthalmic suspension are applied to the ocular surface. Further studies are needed to verify this hypothesis and determine whether this "statistically significant" finding is at all significant from a clinical perspective (i.e., therapeutic benefit, toxicity).…”

“…Given the relatively short precorneal retention time of prednisolone suspension, other strategies could be considered to optimize the therapeutic efficacy of topical corticosteroids: (i) Increase the concentration of the formulation-a 1% preparation of prednisolone acetate produced higher drug concentrations in the eye (cornea, conjunctiva, aqueous humor) compared to 0.125 and 0.5% preparations (6,15); however, 1% is the highest concentration that is commercially available, and further increases in concentration did not augment the therapeutic response in one study of inflammatory keratitis (27); (ii) Increase the viscosity of the formulation-drug concentrations in ocular tissues were higher when prednisolone was coupled with highly viscous polymers such as carboxypolymethylene (28) or carbomer 0.5% (6); (iii) Increase the frequency of administration-reduction in inflammatory cells invading the cornea was significantly better when prednisolone acetate was applied at 1 h compared to 4 h intervals, and was further improved when the drug was applied at 15 min intervals (29); (iv) Consider an alternate corticosteroid-for instance, 0.05% difluprednate administered at a lower frequency than 1% prednisolone acetate is at least as effective in controlling inflammation associated with paracentesis-induced uveitis in dogs (30) or endogenous uveitis in humans (31).…”

“…In each dog, one eye was chosen at random (Excel software) to receive 35 µL (one drop) of 1% prednisolone acetate ophthalmic suspension (Sandoz Inc., Princeton, NJ, United States), while the other eye received 70 µL (two drops), and this selection was kept constant throughout the study. The experiment extended over 13 consecutive days, with topical prednisolone acetate delivered with a pipette at 8:00 a.m. (each day) and tear fluid collected with dye-free Schirmer strips at the following time points (one collection per day): 0 min (i.e., immediately after instillation and blinking), 1,3,5,15,30,45,60,90,120,240,480, and 720 min. At completion of tear collection each day, both eyes were thoroughly rinsed with eyewash (Eye Wash, OcuSOFT Inc., Richmond, TX, United States) to avoid any carryover of prednisolone acetate from 1 day to another.…”

Molecular Expression and Functional Evidence of a Drug Efflux Pump (BCRP) in Human Corneal Epithelial Cells

“…2 Many topically instilled drugs reach the internal segments of the eye through the cornea. 2 As stated by Dey et al (2003), 2 “these drugs include steroids, 31,32 ß-blockers, 33,34 antibiotics, 35,36,37 and nonsteroidal anti-inflammatory agents. 38 ” The cul-de-sac, as a route for topical drug administration, is the most common route of ocular drug delivery.…”

Vehicle Effects on Ocular Drug Bioavailability I: Evaluation of Fluorometholone

“…It does not seem unreasonable to expect that a highly lipophilic steroid such as fluorometholone will tend to concentrate in the epithelial layer, perhaps even reaching a saturation concentration prior to passage through the hydrophilic layers of the cornea. Such a mechanism is not unlikely and was recently speculated upon for other steroidal compounds in a study using prednisolone acetate (9). In such a process, the rate and extent to which the epi-Vol.…”