FP Receptor

In vitro, the three-dimensional (3D) reconstituted human corneal epithelia (HCE) were treated with PBS, BAK-latanoprost, PF-latanoprost, or 0.02% BAK for 24 hours followed or not followed by a 24 hour post incubation recovery period. Cellular viability was evaluated using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test at 24 hours and the apoptotic cells were counted using TUNEL labeling on frozen sections at 24 hours and 24 hours plus 24 hours. [1]

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Considerable apoptosis was triggered in the top layer by benzoalkonium chloride-latanoprost (BAK-latanoprost) and 0.02% BAK, which was linked to a considerable reduction in cell viability. When compared to PBS, the moderate reduction in cell viability caused by Preservative-free latanoprost (PF-latanoprost) and the small number of apoptotic cells identified in the superficial layer did not reach statistical significance [1]. Comparing latanoprost (0.1 μM) to the control, cell viability rose considerably. Simultaneously, 0.1 μM latanoprost can strongly stimulate neurite formation in a manner akin to that of ciliary neurotrophic factor (CNTF) and raise p-Akt and p-mTOR expression levels. By controlling the FP receptor-mediated PI3K-Akt-mTOR signaling cascade, latanoprost can stimulate neurite growth [3]. Latanoprost (0.03 or 0.3 μg/mL) and bimatoprost (75% ± 27% and 75% ± 24%, respectively) enhanced MMP-9 activity in human CBSM cells [4].

In beagle dogs, one drop of latanoprost results in significant miosis, peripheral iris lordosis, iridocorneal angle narrowing, and anterior chamber shallowing. Pupil diameter, ACA, and AOD (mean) decreased by 84%, 14%, and 16%, respectively, following the use of latanoprost [2].

Differentiated RGC-5 cells were treated with latanoprost at different concentrations (0.1–10 μM). After treatment with latanoprost and/or inhibitors for 24 h, cell viability was evaluated using a cell counting kit-8 (CCK-8) (WST-8, Dojindo, Japan). The CCK-8 was used to count living cells by combining WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium,monosodium salt] and 1-methoxy PMS. According to the supplier’s recommendations, 10 μl of kit reagent was added to the cells, treated as described above, in 96-well plates and incubated for 3 h. Cell viability was assayed by reading the absorbance at 450 nm on a 96-well plate reader. The absorbance reading was subtracted from background control. All experiments were performed in three wells on five separate experiments[2].

Thirty-five normal female beagle dogs were assessed using anterior segment optical coherence tomography (AS-OCT). One eye of each dog was scanned with the AS-OCT in the superotemporal quadrant. One drop of latanoprost 0.005% was applied topically, and the OCT scan was repeated 30 min later. Images were imported into ImageJ, and pupil diameter, anterior chamber angle, angle opening distance, angle recess area (ARA), anterior chamber hemifield, and anterior chamber depth were measured.[3]

Absorption, Distribution and Excretion
This drug is rapidly absorbed by the cornea in the form of an isopropyl ester prodrug, followed by hydrolysis and activation. A small amount of the drug is absorbed systemically. The peak plasma concentration (Cmax) of Talampicillin in systemic circulation is reached 5 minutes after administration, measured at 53 pg/mL. The peak plasma concentration in the aqueous humor is reached within 2 hours after administration, estimated at 15-30 ng/mL. Talampicillin is primarily excreted via the kidneys after hepatic β-oxidative metabolism. Approximately 88% of the dose of Talampicillin is excreted in the urine after topical administration. Approximately 15% of the dose has been reported to be excreted in the feces. The volume of distribution of Talampicillin is 0.16 ± 0.02 L/kg. The activated acid form of Talampicillin is detectable in the aqueous humor within the first 4 hours after administration, while it is only detectable in plasma within 1 hour after ocular administration. This drug is more lipophilic than its parent prostaglandin and readily penetrates the cornea. Studies have shown that it can cross the rat placenta. The systemic clearance rate of Talampicillin is 7 mL/min/kg. Following corneal absorption, the prodrug is activated by esterase hydrolysis, converting it into the pharmacologically active drug. A small amount of the drug that enters the bloodstream is metabolized in the liver, converting to 1,2-dinor and 1,2,3,4-tetranor metabolites via fatty acid β-oxidation. The elimination half-life of Talampicillin from plasma is approximately 17 minutes. The elimination half-life of Talampicillin from the eye is estimated to be 2–3 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the use of Talampicillin during lactation. Due to its short half-life, it is unlikely to enter the infant's bloodstream and will not cause any adverse effects on breastfed infants. Professional guidelines consider the use of prostaglandin eye drops during lactation to be acceptable. To significantly reduce the amount of medication that enters breast milk after using eye drops, press your finger against the tear duct near the corner of your eye for at least 1 minute, then blot away any excess medication with absorbent paper.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
The plasma protein binding rate of Talampicillin is approximately 90%.

[1]. In vitro and in vivo comparative toxicological study of a new preservative-free latanoprost formulation. Invest Ophthalmol Vis Sci. 2012 Dec 13;53(13):8172-80.

[2]. Latanoprost promotes neurite outgrowth in differentiated RGC-5 cells via the PI3K-Akt-mTOR signaling pathway. Cell Mol Neurobiol. 2011 May;31(4):597-604.

[3]. The effect of topical latanoprost on anterior segment anatomic relationships in normal dogs. Vet Ophthalmol. 2013 Sep;16(5):370-6.

[4]. Effect of bimatoprost, latanoprost, and unoprostone on matrix metalloproteinases and their inhibitors in human ciliary body smooth muscle cells. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5259-65.

[5]. Prostaglandin Subtype-Selective and Non-Selective IOP-Lowering Comparison in Monkeys.

Latamprost is a prostaglandin Fα, an isopropyl ester prodrug of Talampicillin free acid. It is used to treat open-angle glaucoma and ocular hypertension. It has multiple effects, including anti-glaucoma, antihypertensive, EC 4.2.1.1 (carbonic anhydrase) inhibitor, and prodrug activity. It is a prostaglandin Fα, triol, and isopropyl ester. Its function is related to Talampicillin free acid. Latamprost is a prodrug analog of prostaglandin F2α used to treat elevated intraocular pressure. It was initially approved by the U.S. Food and Drug Administration (FDA) in 1998. Latamprost was the first topical prostaglandin F2α analog for the treatment of glaucoma. Studies have shown that Talampicillin is well-tolerated, and its use generally does not cause systemic adverse reactions like other drugs used to treat elevated intraocular pressure (such as timolol). Another advantage of Talampicillin is that it can be administered once daily. Latamprost is a prostaglandin analog.
Talampicillin is a prostaglandin F2α analog and a prostaglandin-selective FP receptor agonist with intraocular pressure-lowering effects. Talampicillin increases uveal-scleral outflow, thereby lowering intraocular pressure.
A prostaglandin F analog used to treat elevated intraocular pressure in patients with glaucoma.
See also: Talampicillin; Netasudil dimethsulfate (component); Talampicillin; Timolol maleate (component); Talampicillin; Netasudil mesylate (component).

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Indications
Talampicillin is indicated for lowering intraocular pressure in patients diagnosed with open-angle glaucoma or high intraocular pressure. It can be used as monotherapy or in combination with netasudil or timolol. In Canada, Talampicillin is also indicated for the treatment of elevated intraocular pressure in angle-closure glaucoma patients who have undergone peripheral iridotomy or laser iridotomy.
Glaucoma Treatment

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Mechanism of Action
Elevated intraocular pressure (IOP) increases the risk of glaucomatous visual field defects. The higher the IOP, the greater the risk of optic nerve damage and visual field defects. Talampicillin selectively stimulates prostaglandin F2α receptors, thereby reducing IOP by increasing aqueous humor outflow, which is typically associated with elevated IOP. Possible specific mechanisms underlying this increased aqueous humor outflow include extracellular matrix remodeling and regulation by matrix metalloproteinases. These effects lead to increased tissue permeability associated with the aqueous humor outflow pathway, potentially altering aqueous humor outflow resistance and/or outflow rate.

C26H40O5

432.6

432.287

C, 72.19; H, 9.32; O, 18.49

130209-82-4

41639-83-2 (acid); 130209-82-4; 130209-82-4 (ethanol solution)

5311221

Colorless to light yellow liquid at room temperature

1.1±0.1 g/cm3

583.8±50.0 °C at 760 mmHg

188.3±23.6 °C

0.0±1.7 mmHg at 25°C

1.538

3.65

3

5

14

31

526

5

O=C(OC(C)C)CCC/C=C\C[C@@H]1[C@@H](CC[C@@H](O)CCC2=CC=CC=C2)[C@H](O)C[C@@H]1O

GGXICVAJURFBLW-CEYXHVGTSA-N

InChI=1S/C26H40O5/c1-19(2)31-26(30)13-9-4-3-8-12-22-23(25(29)18-24(22)28)17-16-21(27)15-14-20-10-6-5-7-11-20/h3,5-8,10-11,19,21-25,27-29H,4,9,12-18H2,1-2H3/b8-3-/t21-,22+,23+,24-,25+/m0/s1

propan-2-yl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate

PHXA41; PHXA-41; PHXA 41; XA34; XA-34; XA 34; Latanoprost, Xalatan, Catioprost; IYUZEH;

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)

H2O : ~100 mg/mL (~231.17 mM)
Ethanol : ~100 mg/mL (~231.17 mM)
DMSO : ≥ 100 mg/mL (~231.17 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.81 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 20.8 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 3: ≥ 2.08 mg/mL (4.81 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (231.17 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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