Abstract
Purpose: To compare the dose–response profiles of bimatoprost sustained-release implant (Bimatoprost SR) and topical bimatoprost in lowering intraocular pressure (IOP) in normotensive beagle dogs.Methods: In 1 study, topical bimatoprost 0.001%, 0.01%, or 0.1% was administered twice daily in the study eye for 5 days. IOP was measured at baseline and up to hour 6 each day. Other studies evaluated the IOP response to a single administration of Bimatoprost SR at dose strengths ranging from 8 to 120 μg. IOP was measured before implant administration and during 3 months of follow-up; IOP in response to topical bimatoprost 0.03% was measured prestudy as an internal control.Results: Mean percentage decrease in IOP from baseline at hour 6 (peak effect) across study days was 15.7%, 36.1%, and 24.8% (2.8, 7.0, and 4.0 mmHg) in animals treated with topical bimatoprost 0.001%, 0.01%, and 0.1%, respectively. After Bimatoprost SR administration, mean percentage decrease in IOP from baseline across 3 months consistently increased with increasing dose strength and was 38.7% (7.2 mmHg) with Bimatoprost SR 120 μg. Mean percentage IOP decrease with topical bimatoprost 0.03% was 27.6% (5.9 mmHg).Conclusions: Topical bimatoprost demonstrated a U-shaped dose–response curve; increasing the bimatoprost concentration to 0.1% resulted in reduced IOP-lowering efficacy. In contrast, the dose–response curve for Bimatoprost SR showed consistently greater IOP lowering as the dose strength increased, with the dose strength producing maximum IOP lowering not yet determined. At 60- and 120-μg dose strengths, Bimatoprost SR produced greater IOP reductions than were achieved with topical dosing.
Highlights
Topical prostaglandin analogs (PGAs) are commonly used as first-line therapy in glaucoma and ocular hypertension.[1,2] These medications are well tolerated and reduce intraocular pressure (IOP) more effectively than other classes of topical IOP-lowering medications.[3,4]There is a ceiling effect in the IOP lowering produced by the topical PGAs in humans, that is, a leveling off of the effect on IOP despite an increase in drug exposure
Mean percentage IOP lowering increased from 15.7% to 36.1% as the bimatoprost concentration increased from 0.001% to 0.01%, but a decrease in IOP-lowering efficacy occurred as the bimatoprost concentration was further increased to 0.1%, and mean percentage IOP lowering decreased to 24.8% (Fig. 2)
In the studies reported here, the IOP-lowering efficacy of topical bimatoprost in normotensive beagle dogs was maximal at a bimatoprost concentration of 0.01%, and efficacy was reduced when the bimatoprost concentration was increased to 0.1%
Summary
Topical prostaglandin analogs (PGAs) are commonly used as first-line therapy in glaucoma and ocular hypertension.[1,2] These medications (eg, latanoprost, tafluprost, travoprost, and the prostamide bimatoprost) are well tolerated and reduce intraocular pressure (IOP) more effectively than other classes of topical IOP-lowering medications.[3,4]. There is a ceiling effect in the IOP lowering produced by the topical PGAs in humans, that is, a leveling off of the effect on IOP despite an increase in drug exposure. Beyond a certain point, increasing drug exposure, either by increasing the concentration of PGA administered or by increasing the dosing frequency, does not increase IOP-lowering efficacy, and can result in a decrease in IOP lowering and a U-shaped dose–response curve. At month 6, the 10 am mean reduction in IOP from baseline was 8.1 mmHg (32.8%) with bimatoprost
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