Otologic - Corticosteroids and anti-infectives in combination.

Orbifloxacin is a synthetic broad-spectrum bactericidal agent classified as a quinolone carboxylic acid derivative, or more specifically, a fluoroquinolone. The bactericidal action of orbifloxacin results from interference with the enzymes DNA topoisomerase II (DNA-gyrase) and DNA topoisomerase IV which are needed for the synthesis and maintenance of bacterial DNA. Such impairment disrupts replication of the bacterial cell, leading to rapid cell death. The rapidity and extent of killing are directly proportional to the drug concentration. Orbifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative organisms.

Mometasone furoate is a corticosteroid with high topical potency but little systemic effect. Like other topical corticosteroids, it has anti-inflammatory and anti-pruritic properties.

Posaconazole is a broad-spectrum triazole antifungal agent. The mechanism by which posaconazole exerts fungicidal action involves the selective inhibition of the enzyme lanosterol 14-demethylase (CYP51) involved in ergosterol biosynthesis in yeasts and filamentous fungi. In in vitro tests, posaconazole has shown fungicidal activity against most of the approximately 7,000 strains of yeast and filamentous fungi tested. Posaconazole is 40 – 100 times more potent in vitro against Malassezia pachydermatis than clotrimazole, miconazole and nystatin.

Resistance to fluoroquinolones occurs by chromosomal mutation with three mechanisms: Decrease of the bacterial wall permeability, expression of efflux pump, or mutation of enzymes responsible for the molecule’s binding site. Cross-resistance across the fluoroquinolone class of antibiotics is common. Malassezia pachydermatis resistance to azoles, including posaconazole, has not been reported.

The in vitro activity of orbifloxacin against pathogens isolated from clinical cases of canine otitis externa in an EU field trial conducted in 2000 - 2001 was:

Systemic absorption of the active ingredients was determined in single-dose studies with [14C]-orbifloxacin, [3H]-mometasone furoate and [14C]-posaconazole contained within the Posatex formulation and placed into the ear canals of normal Beagle dogs. Most of the absorption occurred in the first few days after administration. The extent of percutaneous absorption of topical medications is determined by many factors including the integrity of the epidermal barrier. Inflammation can increase the percutaneous absorption of veterinary medicinal products.