MAY 21, 2010
This prospective, randomized, double-masked study evaluated the efficacy and safety of bimatoprost 0.01%, 0.0125% and 0.03%. Bimatoprost 0.01% is a new formulation with a reduced bimatoprost concentration but increased benzakonium chloride (BAK)concentration. It is designed to maintain the IOP-lowering efficacy of bimatoprost 0.03% with an improved safety profile.
The authors randomized 561 patients with glaucoma or ocular hypertension to receive once-daily bimatoprost 0.01%, 0.0125% or 0.03% for 12 months. Bimatoprost 0.01%was as effective as bimatoprost 0.03% at lowering IOP and demonstrated improved tolerability, including less frequent and severe conjunctival hyperemia. The overall incidence of treatment-related adverse events was reduced significantly in the bimatoprost 0.01% and bimatoprost 0.0125% groups compared with the bimatoprost 0.03% group (P ≤ .034) ), but bimatoprost 0.01% demonstrated a better benefit-to-risk ratio than bimatoprost 0.0125%.
Topical prostaglandin analogs, especially bimatoprost, are associated with significant conjunctiva hyperemia and other related effects. While the preservatives used in different formulations contribute to ocular surface disease, these same preservatives enhance the bioavailability and efficacy of topical therapy. Bimatoprost does not penetrate the cornea well compared with other prostaglandin analogs. As a result, its approved concentration is relatively high, which may reduce its tolerability.
This study shows that decreasing the concentration of bimatoprost by a factor of three doesn't reduce the drug's efficacy as long as corneal penetration is enhanced by increasing the amount of BAK in the formulation. It also shows that despite the increased amount of preservative, tolerability can be increased significantly.
These findings suggest that new formulations of topical glaucoma medications should aim to intelligently balance the concentration of both the active ingredient and preservatives to enhance tolerability.