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Latanoprostene bunod API Manufacturers & Suppliers

General Description:

Latanoprostene bunod, identified by CAS number 860005-21-6, is a notable compound with significant therapeutic applications. Latanoprostene Bunod has been used in trials studying the treatment of Glaucoma, Ocular Hypertension, Open-Angle Glaucoma, Open Angle Glaucoma, and Intraocular Pressure. As of November 2, 2017 the FDA approved Bausch + Lomb's Vyzulta (latanoprostene bunod opthalmic solution), 0.024% for the indication of reducing intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Latanoprostene bunod is the first prostaglandin analog with one of its metabolites being nitric oxide (NO). The novelty of this agent subsequently lies in the proposed dual mechanism of action that stems from both its prostaglandin F2-alpha analog latanoprost acid metabolite and its ability to donate NO for proposed tissue/cell relaxation effects. In comparison, both latanoprost and latanoprostene bunod contain a latanoprost acid backbone. Conversely however, latanoprostene bunod integrates an NO-donating moiety in lieu of the isopropyl ester typically found in latanoprost.

Indications:

This drug is primarily indicated for: Latanoprostene bunod opthalmic solution is indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Latanoprostene bunod undergoes metabolic processing primarily in: Upon topical administration at the ocular surface, latanoprostene bunod undergoes rapid carboxyl ester hydrolysis by endogenous corneal esterases into latanoprost acid and butanediol mononitrate . After the latanoprost acid reaches the systemic circulation, it is largely metabolized by the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites by way of fatty acid beta-oxidation . The butanediol monohidrate undergoes further metabolism (reduction) to 1,4-butanediol and nitric oxide (NO). Furthermore, this 1,4-butanediol metabolite is further oxidized to succinic acid that is subsequently then primarily taken up as a component in the tricarboxylic acid (TCA) cycle in cellular aerobic respiration . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Latanoprostene bunod are crucial for its therapeutic efficacy: In a study with 22 healthy subjects monitored for 28 days, there were no quantifiable plasma concentrations of latanoprostene bunod (Lower Limit Of Quantitation, LLOQ, of 10.0 pg/mL) or butanediol mononitrate (LLOQ of 200 pg/mL) post daily dose of one drop bilaterally in the morning on Day 1 and 28 . The mean time of maximum plasma concentration (Tmax) for latanoprost acid was about 5 minutes post dosage on both Day 1 and 28 of therapy . The mean maximum plasma concentrations (Cmax) of latanoprost acid (LLOQ of 30 pg/mL) were 59.1 pg/mL on Day 1 and 28, respectively . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Latanoprostene bunod is an important consideration for its dosing schedule: The half-life after application of latanoprostene bunod in rabbits was 1.8 hours in cornea, 2.1 hours in aqueous humor, and 4.6 hours in the iris/ciliary body . This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Latanoprostene bunod from the body primarily occurs through: The latanoprost acid component of latanoprostene bunod is predominantly metabolized by the liver and excreted primarily in the urine . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Latanoprostene bunod is distributed throughout the body with a volume of distribution of: Unfortunately there have been no formal ocular distribution studies performed in humans at this time . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Latanoprostene bunod is a critical factor in determining its safe and effective dosage: Since latanoprost acid plasma concentration dropped below the LLOQ (Lower Limit Of Quantitation) of 30 pg/mL in the majority of study subjects by 15 minutes following ordinary ocular administration, the elimination of latanoprost acid from human plasma is considered rapid . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Latanoprostene bunod exerts its therapeutic effects through: Upon applying an appropriate dose of latanoprost bunod, reduction in intraocular pressure begins approximately 1 to 3 hours later with a maximum intraocular pressure reduction effect demonstrated after 11 to 13 hours . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Latanoprostene bunod functions by: Open-angle glaucoma (OAG) is a medical condition that is associated with progressive visual field damage and the loss of vision . Occular hypertension (OHT) is considered a key risk factor for OAG and reducing intraocular pressure (IOP) and being able to maintain unique and appropriate target IOPs for various different patients having OHT can delay or prevent the onset of primary OAG or slow the disease progression of established glaucoma . Ordinary physiological IOP results from aqueous humor produced by the ocular ciliary body and its outflow through a) the trabecular meshwork (TM) and Schlemm's canal (SC) in what is called the conventional pathway, and b) the uveoscleral pathway via the ciliary muscle/choroid/sclera in what is refered to as the unconventional pathway . In patients with OHT or OAG there is increased resistance to aqueous humor outflow by way of the TM/SC pathway, which causes increased IOP. This increase in IOP is believed to be the cause of mechanical stress on the posterior structures of the eye which can result in the dysfunction of optic nerve fibers and the destruction of retinal ganglion cells - all of which ultimately contributes to vision loss . As there is no cure for glaucoma, therapeutic management is predominantly focused on minimizing disease progression and clinical sequelae via the reduction and maintainenance of appropriate target IOPs . Subsequently, latanoprostene bunod is thought to lower intraocular pressure via a dual mechanism of action since the medication is metabolized into two relevant moieties upon administration: (1) latanoprost acid, and (2) butanediol mononitrate . As a prostaglandin F2-alpha analog , the latanoprost acid moiety operates as a selective PGF2-alpha (FP) receptor agonist . Since FP receptors occur in the ciliary muscle, ciliary epithelium, and sclera the latanoprost acid moiety primarily acts in the uveoscleral pathway where it increases the expression of matrix metalloproteinases (MMPs) like MMP-1, -3, and -9 which promote the degradation of collagen types I, III, and IV in the longitudinal bundles of the ciliary musicle and surrounding sclera . The resultant extracellular matrix remodeling of the ciliary muscle consequently produces reduced outflow resistance via increased permeability and increased aqueous humor outflow through the uveoscleral route . Conversely, the butanediol mononitrate undergoes further metabolism to NO and an inactive 1,4-butanediol moiety. As a gas that can freely diffuse across plasma membranes, it is proposed that the relaxing effect of NO to induce reductions in the cell volume and contractility of vascular smooth muscle like cells is dependant upon activation of the sGC/cGMP/PKG cascade pathway. NO released from butanediol mononitrate consequently enters the cells of the TM and inner wall of SC, causing decreases in myosin light chain-2 phosphorylation, increased phosphorylation of large-conductance calcium-activated potassium (BKCa) channels, and a subsequent efflux of potassium ions through such BKCa channels. All of these changes serve to decrease the cell contractility and volume, as well as to rearrange the actin cytoskeleton of the TM and SC cells. These biomechanical changes ultimately allow for enhanced conventional outflow of aqueous humor . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Latanoprostene bunod belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid, classified under the direct parent group Prostaglandins and related compounds. This compound is a part of the Organic compounds, falling under the Lipids and lipid-like molecules superclass, and categorized within the Fatty Acyls class, specifically within the Eicosanoids subclass.

Categories:

Latanoprostene bunod is categorized under the following therapeutic classes: Antiglaucoma Preparations and Miotics, Autacoids, Biological Factors, Drugs that are Mainly Renally Excreted, Eicosanoids, Fatty Acids, Fatty Acids, Unsaturated, Inflammation Mediators, Lipids, OATP2B1/SLCO2B1 substrates, Ophthalmologicals, Prostaglandin analogs reducing intraocular pressure (IOP), Prostaglandins, Prostaglandins, Synthetic, Sensory Organs. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.