Augmentation of the ocular penetration of dexamethasone with β‐blocker and α‐agonist co‐administration

Abstract

AbstractPurpose This study evaluated the ocular penetration of the radiolabelled corticosteroid 3H‐dexamethasone after topical administrations of the β‐blocker Ophtim®(0.5% timolol) and the α‐agonist Iopidine®(1% apraclonidine) alone or in combination in pigmented rabbits.Methods Animals were randomized in 4 treatment groups : Ophtim® or Iopidine®, or both of them, or NaCl 0.9%, first in 3 3‐min apart topical administrations of 30 µL, followed by a single 30 µL instillation of 3H‐dexamethasone (5 µCi), in both eyes and then in a single instillation every 2 hours, each also followed by a single instillation of 3H‐dexamethasone. At 1, 2 and 8 hours after the first instillation, animals were euthanized and the aqueous humor, vitreous, retina and choroid were taken to determine 3H‐dexamethasone concentrations with a liquid scintillation counter.Results 3H‐dexamethasone was detected in all tested ocular matrices, regardless of the pre‐treatment. The 3H‐dexamethasone concentrations tended to moderately increase in ocular tissues from animals pre‐treated with either Ophtim® or Iopidine®. However, the preliminary topical administration of Ophtim® associated to Iopidine® resulted in a significant increase in the 3H‐dexamethasone concentrations in sampled ocular tissues, including a nearly 3‐fold increase in aqueous humor, compared with NaCl 0.9%.Conclusion In conclusion, the association of the β‐blocker Ophtim® with the α‐agonist Iopidine® in multiples instillations prior to 3H‐dexamethasone instillation increased the ocular penetration of the radiolabelled corticosteroid. Commercial interest