Abstract
Purpose: To explore the ocular distribution of bimatoprost after intracameral administration of a biodegradable sustained-release bimatoprost implant (Bimatoprost SR) versus repeated topical administration of bimatoprost 0.03% ophthalmic solution in dogs. Bimatoprost SR and topical bimatoprost 0.03% previously were shown to have similar intraocular pressure-lowering effects in humans in a phase 1/2 clinical trial.Methods: Twenty-four beagle dogs received either once-daily topical bimatoprost 0.03% for 7 days or a bilateral intracameral administration of Bimatoprost SR (15 μg). At predetermined time points, ocular tissues were collected and concentrations of bimatoprost and bimatoprost acid were quantified using liquid chromatography–tandem mass spectrometry.Results: Bimatoprost SR administration enhanced delivery of study drug to a site of action [iris–ciliary body (ICB)] compared with topical bimatoprost (Cmax [bimatoprost+bimatoprost acid] = 18,200 and 4.13 ng/g, respectively). However, distribution of drug to tissues associated with prostaglandin analog (PGA)-related side effects (i.e., bulbar conjunctiva, eyelid margins, and periorbital fat) was limited following Bimatoprost SR administration (Cmax [bimatoprost+bimatoprost acid] = BLQ [beneath the limit of quantitation] to 0.354 ng/g) compared with topical dosing (Cmax [bimatoprost+bimatoprost acid] = 36.6–2,110 ng/g).Conclusions: Bimatoprost SR administration in dogs selectively delivered drug to the ICB with low or undetectable drug levels in ocular surface and extraocular tissues. Use of Bimatoprost SR for glaucoma treatment may reduce the incidence of adverse events typically associated with topical PGAs by targeting bimatoprost delivery to the key site of action of the PGA class and reducing exposure to off-target tissues.
Highlights
Glaucoma, a group of ocular disorders with a multifactorial etiology, is characterized by the presence of intraocular pressure (IOP)-associated optic neuropathy.[1]
Distribution of drug to tissues associated with prostaglandin analog (PGA)-related side effects was limited following Bimatoprost SR administration (Cmax [bimatoprost+bimatoprost acid] = BLQ [beneath the limit of quantitation] to 0.354 ng/g) compared with topical dosing (Cmax [bimatoprost+bimatoprost acid] = 36.6–2,110 ng/g)
Following the administration of Bimatoprost SR 15 mg, low or undetectable bimatoprost and bimatoprost acid concentrations were observed in ocular tissues associated with PGA-related adverse events (AEs), such as the bulbar conjunctiva, eyelid margin, periorbital fat, and retina
Summary
A group of ocular disorders with a multifactorial etiology, is characterized by the presence of intraocular pressure (IOP)-associated optic neuropathy.[1]. The principal goal of glaucoma treatment is to reduce IOP and preserve visual function while maintaining patient quality of life.[5] IOP can be lowered with pharmacological treatments, laser treatments, and various minimally invasive or incisional surgical procedures. Pharmacological therapies are currently the most common form of initial intervention. Topical prostaglandin analog (PGA) medications (such as latanoprost, tafluprost, travoprost, and the prostamide bimatoprost) are widely used as first-line therapies due to their proven efficacy, favorable safety profile, and convenient once-daily dosing schedule.[5,6,7,8,9]
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