Rimexolone

Corticosteroids suppress the inflammatory response to a variety of inciting agents of a mechanical, chemical, or immunological nature. They prevent or suppress redness, swelling, tenderness, exudation, cellular infiltration, capillary dilation, fibroblastic proliferation, deposition of collagen and late cicatrization. Placebo controlled clinical studies demonstrated that rimexolone is efficacious for the treatment of anterior chamber inflammation following cataract surgery.

In two controlled clinical trials, rimexolone demonstrated clinical and statistical equivalence to 1% prednisolone acetate in controlling uveitic inflammation. Supportive studies have confirmed the anti-inflammatory activity of rimexolone in steroid responsive ocular inflammation.

Corticosteroids are capable of producing a rise in intraocular pressure in susceptible individuals. In a controlled 6 week study of steroid responsive subjects the time to raise intraocular pressure was similar for rimexolone and 0.1% fluorometholone given four times daily.

As with other topically administered drugs, rimexolone is absorbed systemically. Studies in normal volunteers dosed bilaterally once every hour during waking hours for one week have demonstrated maximal serum concentrations ranging from less than 80 pg/mL to approximately 460 pg/mL. The mean maximal serum concentrations were approximately 150 pg/mL (n=15). Serum concentrations were at or near steady state on day one of the dosing regimen. After decreasing the dosing frequency to once every two hours while awake during the second week of administration, mean maximal serum concentrations were approximately 100 pg/mL. The serum half-life of rimexolone could not be reliably estimated due to the large number of samples below the quantitation limit of the assay (80 pg/mL). However, based on the time required to reach steady-state, the halflife appears to be short (1-2 hours).

Based upon in vivo and in vitro preclinical metabolism studies and on in vitro results with human liver preparations, Rimexolone undergoes extensive metabolism with primary (>80%) excretion via the faeces. Metabolites have been shown to be less active than parent drug, or inactive in human glucocorticoid binding assays.

Carcinogenesis, mutagenesis, impairment of fertility: Rimexolone has been shown to be not mutagenic in a battery of in vitro and in vivo mutagenicity assays. Fertility and reproductive capability was not impaired in a study in rats with plasma levels (42 nanograms/mL) approximately 200 times those obtained in clinical studies after topical administration (<0.2 nanogram/mL). Long-term studies have not been conducted in animals to evaluate the carcinogenic potential of rimexolone.

Rimexolone has been shown to be teratogenic and embryotoxic in rabbits following subcutaneous administration, but was not teratogenic or embryotoxic in rats. Corticosteroids are recognized to cause foetal resorptions and malformations in animals, though the association in humans has not been firmly established.