RESUMO
Purpose: This article aims to describe a preclinical proof of concept for a novel once-a-day (OD) brimonidine ophthalmic nanosuspension. Methods: The preclinical proof of concept was established using New Zealand white rabbits as animal models. Dose-finding, multiple-dose efficacy, ocular pharmacokinetic, and hemodynamic studies were performed in normotensive rabbits. Steroid-induced ocular hypertension model in rabbits was used to study efficacy in glaucomatous pathophysiology. The test (0.35% OD suspension) and reference (0.15% three times a day [TID] solution) were compared. Results: The intraocular pressure (IOP) reduction was sustained for 0.35% and 0.5% strengths but not for other lower strengths tested or reference strengths. A 0.35% OD suspension reduced IOP >2 mmHg after 24 h of dosing, which was not seen with the reference. After multiple dosing, 0.35% OD suspension reduced IOP by 4-6 mmHg after 24 h, which was comparable to the 0.15% TID reference solution. An ocular pharmacokinetic study showed that the brimonidine was rapidly absorbed and distributed throughout the eye after topical administration. Concentration was higher in tissues with high α2 receptors, such as cornea-conjunctiva, iris/ciliary body, and choroid/retina. The steady-state concentrations in these organs were also significant after 24 h of the last dose. There was an indication of increased plasma levels, so a hemodynamic study was performed to assess any adverse effects. All hemodynamic parameters were normal and no new unusual safety findings were observed. Conclusions: The study demonstrated that the novel brimonidine 0.35% ophthalmic nanosuspension is both safe and effective when administered OD and is comparable to the marketed reference formulation administered TID.
RESUMO
BACKGROUND: Apical migration of the gingival margin beyond the cement-enamel junction (CEJ) is called as gingival recession. Various classifications of gingival recession have been proposed to evaluate different degrees of damage to periodontal tissues, but do not consider the condition of the exposed root surface: presence of an identifiable CEJ and presence of root abrasion. Sometimes these lesions may be associated with enamel abrasion. Therefore, the aim of this paper is to propose the new classification of dental surface defects in gingival recession area. METHODS: Two factors were evaluated to set up a classification system: presence (A) or absence (B) of CEJ and presence (+) or absence (-) of dental surface discrepancy caused by abrasion (step). Four classes (A+, A-, B+, and B-) were identified on the basis of these variables. The classification was used on 1,000 gingival recessions to examine the distribution of the four classes. RESULTS: Out of 1,000 exposed root surfaces, 380 showed an identifiable CEJ associated with step (Class A+, 38%); 280 an identifiable CEJ without any associated step (Class A-, 28%); 200 an unidentifiable CEJ with a step (Class B+, 20%); and 140 an unidentifiable CEJ without any associated step (Class B-, 14%). CONCLUSION: The proposed classification describes the dental surface defects that are of paramount importance in diagnosing gingival recession areas which might help in selecting the definite treatment approach.
