1. Bol 303259-x
2. Bol-303259-x
3. Bol303259-x
4. Ncx 116
5. Ncx-116
6. Ncx116
7. Pf 3187207
8. Pf-3187207
9. Pf3187207
1. Vyzulta
2. 860005-21-6
3. Pf-3187207
4. Bol-303259-x
5. Ncx 116
6. Ncx-116
7. 4-nitrooxybutyl (z)-7-[(1r,2r,3r,5s)-3,5-dihydroxy-2-[(3r)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate
8. I6393o0922
9. 4-(nitrooxy)butyl (5z)-7-((1r,2r,3r,5s)-3,5-dihydroxy-2-((3r)-3-hydroxy-5-phenylpentyl)cyclopentyl)hept-5-enoate
10. Vesneo
11. Latanoprostene Bunod [inn]
12. Unii-i6393o0922
13. Latanoprostene Bunod [usan:inn]
14. Lbn
15. Vyzulta (tn)
16. Lbnncx116
17. Gtpl9635
18. Ncx116
19. Chembl2364612
20. Schembl12119560
21. Latanoprostene Bunod [mi]
22. Chebi:177703
23. Latanoprostene Bunod (usan/inn)
24. Dtxsid101027765
25. Latanoprostene Bunod [usan]
26. Bcp29385
27. Latanoprostene Bunod [who-dd]
28. Db11660
29. Hy-19518
30. Latanoprostene Bunod [orange Book]
31. Cs-0015617
32. D10441
33. Q27280492
| Molecular Weight | 507.6 g/mol |
|---|---|
| Molecular Formula | C27H41NO8 |
| XLogP3 | 4.4 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 18 |
| Exact Mass | 507.28321727 g/mol |
| Monoisotopic Mass | 507.28321727 g/mol |
| Topological Polar Surface Area | 142 Ų |
| Heavy Atom Count | 36 |
| Formal Charge | 0 |
| Complexity | 646 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 5 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 1 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
| 1 of 1 | |
|---|---|
| Drug Name | VYZULTA |
| Active Ingredient | LATANOPROSTENE BUNOD |
| Company | BAUSCH AND LOMB (Application Number: N207795. Patents: 6211233, 7273946, 7629345, 7910767, 8058467) |
Latanoprostene bunod opthalmic solution is indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
FDA Label
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.
S - Sensory organs
S01 - Ophthalmologicals
S01E - Antiglaucoma preparations and miotics
S01EE - Prostaglandin analogues
S01EE06 - Latanoprostene bunod
Absorption
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.
Route of Elimination
The latanoprost acid component of latanoprostene bunod is predominantly metabolized by the liver and excreted primarily in the urine.
Volume of Distribution
Unfortunately there have been no formal ocular distribution studies performed in humans at this time.
Clearance
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.
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.
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.
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.
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