- Protocol for evaluation of topical ophthalmic drug products in different compartments of fresh eye tissues in a rabbit model. [Journal Article]J Pharmacol Toxicol Methods 2019 Mar - Apr; 96:9-14JP
- Topical ophthalmic drugs are the most commonly used dosage form to treat diseases of the anterior segment of the eye. Although this dosage form has the advantages of ease of application, small volume dose, and rapid action and is largely devoid of systemic adverse effects, the bioavailability is low due to pre-corneal anatomical barriers and the nature of the drug formulation itself. Some complex…
Topical ophthalmic drugs are the most commonly used dosage form to treat diseases of the anterior segment of the eye. Although this dosage form has the advantages of ease of application, small volume dose, and rapid action and is largely devoid of systemic adverse effects, the bioavailability is low due to pre-corneal anatomical barriers and the nature of the drug formulation itself. Some complex generic formulations (suspensions, ointments, gels) for topical ophthalmic products face impediments to rapid regulatory approval because of the complex nature of the formulations and difficulties in determining bioequivalence with the innovator product. Clinical endpoint bioequivalence studies of ophthalmic products in humans are challenging due to inaccessibility of internal compartments of eye, large inter-subject variability that reduces study sensitivity, patient safety issues, and the prohibitively high costs of these types of clinical studies. Because of its ocular anatomical similarity to human eye, rabbits are frequently used as a model in early product development. Generating appropriate animal model data can inform physiological-based pharmacokinetic (PBPK) model building that might eventually replace the need for extensive, expensive preclinical and clinical testing. Little detail was found in the existing literature on sampling and bioanalytical protocols for determining drug concentration in different compartments of fresh eye tissues. This study describes in detail a sampling protocol for evaluating dexamethasone concentration in different tissues of freshly harvested eyes using TobraDex ST topical ophthalmic drug product in a rabbit model.
- Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure. [Review]Adv Ther 2016; 33(4):532-52AT
- Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the deve…
Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the development of glaucoma. The corticosteroid loteprednol etabonate (LE) contains an ester rather than a ketone at the C-20 position, minimizing the potential for side effects, including IOP elevation. In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use. Since then, new LE formulations-including a gel, an ointment, and a suspension of LE in combination with tobramycin-have become commercially available. Multiple studies evaluating the safety and efficacy of LE for inflammatory conditions have been reported, including those requiring longer-term treatment such as photorefractive keratectomy, corneal transplantation, and dry eye disease. We review the available published data on the effect of LE on IOP and report on the cumulative incidence of clinically significant IOP elevations (≥10 mm Hg from baseline) with short-term and long-term LE use. In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.
- Loteprednol Etabonate 0.5%/Tobramycin 0.3% Compared with Dexamethasone 0.1%/Tobramycin 0.3% for the Treatment of Blepharitis. [Randomized Controlled Trial]Ocul Immunol Inflamm 2017; 25(2):267-274OI
- CONCLUSIONS: LE/T was similarly effective in reducing the signs of blepharitis compared with DM/T, but demonstrated a better safety profile with respect to changes in IOP.
- A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis. [Randomized Controlled Trial]Curr Med Res Opin 2012; 28(3):385-94CM
- CONCLUSIONS: Treatment with LE/T was at least as effective as DM/T in Chinese patients with BKC and had a better safety profile with respect to change in IOP.
- Evaluation of clinical efficacy and safety of tobramycin/dexamethasone ophthalmic suspension 0.3%/0.05% compared to azithromycin ophthalmic solution 1% in the treatment of moderate to severe acute blepharitis/blepharoconjunctivitis. [Randomized Controlled Trial]Curr Med Res Opin 2011; 27(1):171-8CM
- CONCLUSIONS: ST provides a fast and effective treatment of acute blepharitis compared to azithromycin. Initial therapy with the combination of tobramycin/dexamethasone provides faster inflammation relief than azithromycin for moderate to severe blepharitis/blepharoconjunctivitis.
- Clinical and antiviral efficacy of an ophthalmic formulation of dexamethasone povidone-iodine in a rabbit model of adenoviral keratoconjunctivitis. [Journal Article]Invest Ophthalmol Vis Sci 2011; 52(1):339-44IO
- CONCLUSIONS: FST-100 was the most efficacious in minimizing the clinical symptoms of adenovirus infection in rabbit eyes. FST-100 and 0.5% cidofovir were both equally effective in reducing viral titers and decreasing the duration of viral shedding. By providing symptomatic relief in addition to reducing infectious virus titers, FST-100 should be a valuable addition to treatment of epidemic adenoviral keratoconjunctivitis.
- Ocular distribution, bactericidal activity and settling characteristics of TobraDex ST ophthalmic suspension compared with TobraDex ophthalmic suspension. [Journal Article]Adv Ther 2008; 25(2):77-88AT
- CONCLUSIONS: TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.
- Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers. [Randomized Controlled Trial]Cornea 2008; 27(1):50-5C
- CONCLUSIONS: Loteprednol/tobramycin was significantly less likely to produce elevations in IOP than was dexamethasone/tobramycin in healthy subjects treated for 28 days. Both loteprednol etabonate/tobramycin and dexamethasone/tobramycin were well tolerated with low risks for systemic AEs and ocular AEs other than elevation in IOP for dexamethasone/tobramycin.