Ocular normotensive monkeys were given Xalatan, 0.0001%, 0.001%, or 0.01% of ombidenepag isopropyl, or a vehicle topically in one eye. The postdosing baseline value set on day 1 was compared to the IOP change following medication administration. In ocular normotensive monkeys, omidenepag isopropyl likewise exhibits significant and dose-dependent effects on IOP, with mean maximal IOP reductions of 2.4 ± 0.6, 7.6 ± 1.7, and 13.3 ± 1.2 mm Hg at each tested dosage, respectively. At time 0 on day 7, there were notable reductions in IOP for both 0.001% and 0.01% OMDI. In both ocular normotensive and hypertensive animal models, omidenepag isopropyl is hydrolyzed in the eye to become omidenepag (OMD), an EP2 receptor agonist with a notable ocular hypotensive effect[1]. Omidenepag isopropyl decreases intraocular pressure in ocular hypertensive monkeys by enhancing uveoscleral and trabecular outflow[2].

Absorption, Distribution and Excretion
Isopropyl alcohol omeprazole eye drops are absorbed through the cornea and hydrolyzed within the cornea to the active metabolite omeprazole. After instilling one drop of 0.0025% isopropyl alcohol omeprazole eye drops into both eyes for 7 consecutive days, peak plasma concentrations (Cmax) are reached within 10–15 minutes. Since systemic exposures were similar on days 1 and 7, there is no evidence of systemic accumulation of isopropyl alcohol omeprazole. A study comparing the pharmacokinetic parameters of omeprazole in healthy Japanese and Caucasian subjects found no significant differences. The corresponding Cmax in healthy Japanese and Caucasian subjects were 41.5 ± 20.1 and 27.2 ± 10.2 pg/mL, respectively, and the corresponding AUC0–8 h were 26.1 ± 5.7 and 15.3 ± 4.7 h·pg/mL, respectively (mean ± standard deviation).
168 hours after a single eye instillation of 0.03% isopropyl omedepag (5 mcL/eye, 3 mcg/rat), 89% of the administered dose was excreted. Omedepag was primarily excreted in feces (83%) and urine (4%).
No data available.
No data available.
Metabolism/Metabolites

Omedepag isopropyl ester is rapidly metabolized to pharmacologically active omedepag by carboxylesterase-1 following topical ocular administration. In the liver, omedepag is further metabolized via oxidation, N-dealkylation, glucuronidation, sulfate conjugation, or taurine conjugation. CYP3A4 plays an important role in the hepatic metabolism of omedepag.
Biological Half-Life

Half-life data for omedepag isopropyl ester are unavailable. Its active metabolite, omedepag, has an average terminal half-life of approximately 30 minutes.

Protein Binding
Currently, there is no data on the protein binding rate of omedepa isopropyl ester. Its active metabolite, omedepa, has a protein binding rate of 97.8%.

[1]. Pharmacologic Characterization of Omidenepag Isopropyl, a Novel Selective EP2 Receptor Agonist, as an Ocular Hypotensive Agent. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):145-153.

[2]. Effects of a Novel Selective EP2 Receptor Agonist, Omidenepag Isopropyl, on Aqueous Humor Dynamics in Laser-Induced Ocular Hypertensive Monkeys. J Ocul Pharmacol Ther. 2018 Sep;34(7):531-537.

Omidenepag isopropyl ester is a topical intraocular pressure (IOP) lowering agent used to reduce intraocular pressure in patients with glaucoma and high intraocular pressure. Omidenepag isopropyl ester is rapidly metabolized to its active metabolite, omedepa, which has high selectivity and agonistic activity towards prostaglandin E2 (EP2) receptors. Prostaglandin FP receptor agonists (FP agonists), such as latanoprost, are first-line treatments for high IOP and primary open-angle glaucoma; however, not all patients achieve the desired IOP-lowering effect with FP agonists, thus requiring treatment adjustments. In these cases, using EP2 receptor agonists (such as omedepa) is a viable alternative. Omidenepag's IOP-lowering effect is comparable to latanoprost. In 2018, isopropyl omedepa was approved in Japan for the treatment of glaucoma and high IOP. In September 2022, the U.S. Food and Drug Administration (FDA) approved the use of isopropyl omedepa. See also: Omidenepag (containing the active ingredient).

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Indications
Isopropyl omeprazole eye drops (0.002%) are indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or high intraocular pressure.

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Mechanism of Action
Isopropyl omeprazole is a prodrug of omeprazole, a relatively selective prostaglandin E2 (EP2) receptor agonist that reduces intraocular pressure (IOP). Elevated IOP is associated with the risk of visual field defects in glaucoma; the higher the IOP, the greater the likelihood of optic nerve damage and visual field defects. The exact mechanism by which omeprazole lowers IOP is not fully understood; however, studies have shown that omeprazole increases aqueous humor outflow via the conventional pathway and the uveal-scleral pathway by binding to EP2 receptors. EP2 receptors are present in various ocular tissues involved in aqueous humor dynamics, such as the ciliary muscle (CM) and trabecular meshwork (TM). Activation of the EP2 receptor may lead to increased intracellular cyclic adenosine monophosphate (cAMP) levels, resulting in relaxation of the ciliary muscle and trabecular meshwork.

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Pharmacodynamics
Isopropyl omedepa is rapidly hydrolyzed to its active metabolite, omedepa. Omedepa has a high affinity for the prostaglandin E2 (EP2) receptor, with a strong binding affinity of 3.6 nM (K_i). Omedepa exhibits high agonistic activity towards the EP2 receptor, with an EC50 of 8.3 nM, and has no effect on other receptors, such as the prostaglandin E1 (EP1) receptor and the prostaglandin F receptor (FP). Unlike omedepa, isopropyl omedepa has a weaker or no affinity for prostaglandin receptors. Use of isopropyl omedepa may cause pigmentation of the iris, periorbital tissues, and eyelashes. Iris pigmentation may be permanent, while periorbital and eyelash pigmentation is reversible in most patients. Patients receiving isopropyl omedepa treatment may also experience eyelash changes and eye inflammation. Furthermore, in patients with intraocular lenses, the use of isopropyl omedepa may cause macular edema.

C26H28N6O4S

520.6033

520.189

1187451-19-9

44230999

White to off-white solid powder

1.3±0.1 g/cm3

709.9±70.0 °C at 760 mmHg

383.1±35.7 °C

0.0±2.3 mmHg at 25°C

1.641

3.26

1

9

12

37

814

0

VIQCWEGEHRBLAC-UHFFFAOYSA-N

InChI=1S/C26H28N6O4S/c1-20(2)36-26(33)17-28-25-8-3-6-22(30-25)19-31(37(34,35)24-7-4-13-27-16-24)18-21-9-11-23(12-10-21)32-15-5-14-29-32/h3-16,20H,17-19H2,1-2H3,(H,28,30)

Propan-2-yl N-(6-((N-((4-(1H-pyrazol-1-yl)phenyl)methyl)pyridine-3-sulfonamido)methyl)pyridin-2-yl)glycinate

DE-117 DE 117 DE117

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~96.04 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)