Absorption, Distribution and Excretion
Absorbed well after ocular administration. Metabolism/Metabolites Dipifluridine is converted to adrenaline in the human eye via enzymatic hydrolysis.

[1]. Dipivefrin and epinephrine treatment of elevated intraocular pressure: a comparative study. Arch Ophthalmol. 1979 Oct;97(10):1865-6.

[2]. Thermoresponsive sol-gel improves ocular bioavailability of Dipivefrin hydrochloride and potentially reduces the elevated intraocular pressure in vivo. Saudi Pharm J. 2020 Aug;28(8):1019-1029.

Depivalline is a dipentalyl ester of (+-)-adrenaline (racemic adrenaline). As a prodrug of adrenaline, its hydrochloride salt is used topically as eye drops to lower intraocular pressure, used to treat open-angle glaucoma or ocular hypertension. It has multiple functions, including as a prodrug, adrenergic agonist, sympathomimetic agent, antiglaucoma drug, and ophthalmic medication. It belongs to the ethanolamine class of compounds and is a neopentalyl ester. Its function is related to adrenaline. It is the conjugate base of depivalline (1+). Depivalline is a prodrug of adrenaline used to treat glaucoma. It is provided in the form of ophthalmic solutions (eye drops). Depivalline is an adrenergic receptor agonist. The mechanism of action of depivalline is as an adrenergic agonist. Depivalline is an ester prodrug of adrenaline with sympathomimetic activity. Due to its lipophilic nature, dipiformin more readily penetrates the anterior chamber of the eye and hydrolyzes into epinephrine upon topical application. Epinephrine is an adrenergic agonist that promotes aqueous humor outflow and reduces aqueous humor production through vasoconstriction. The end result is a reduction in intraocular pressure.

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Drug Indications
Dipirin is a prodrug used for the initial treatment of chronic open-angle glaucoma to control intraocular pressure.
FDA Label

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Mechanism of Action
Dipirin is a prodrug that has little pharmacological activity before being hydrolyzed into epinephrine in the human eye. The released epinephrine is an adrenergic agonist whose mechanism of action appears to be through stimulation of α- and/or β2-adrenergic receptors, thereby reducing aqueous humor production and increasing aqueous humor outflow. Dipiformin prodrug delivery systems offer a more efficient route of epinephrine therapy with fewer side effects compared to traditional epinephrine therapy.

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Pharmacodynamics
Dipiforin belongs to the prodrug class of drugs. Prodrugs themselves are usually inactive and require biotransformation to exert their therapeutic effect. These transformations aim to improve absorption, reduce side effects, enhance stability and comfort, thereby making the parent compound a more effective drug. Increased absorption makes prodrugs a more efficient delivery system for the parent drug, as less drug is needed to produce the desired therapeutic effect. Dipiforin is a prodrug of adrenaline, formed by the diesterization of adrenaline and neovaleric acid. Adding a neovaleric group to the adrenaline molecule enhances its lipophilicity, thereby improving its ability to enter the anterior chamber.

C19H29NO5

351.4373

351.205

52365-63-6

Dipivefrin hydrochloride;64019-93-8

3105

Typically exists as solid at room temperature

1.097 g/cm3

473.7ºC at 760 mmHg

146-147°

240.3ºC

1.511

3.233

2

6

9

25

463

0

CNCC(C1C=CC(OC(C(C)(C)C)=O)=C(OC(C(C)(C)C)=O)C=1)O

OCUJLLGVOUDECM-UHFFFAOYSA-N

InChI=1S/C19H29NO5/c1-18(2,3)16(22)24-14-9-8-12(13(21)11-20-7)10-15(14)25-17(23)19(4,5)6/h8-10,13,20-21H,11H2,1-7H3

4-(1-hydroxy-2-(methylamino)ethyl)-1,2-phenylene bis(2,2-dimethylpropanoate)

Dipivefrinum DipivefrinaK 30081 K-30081K30081 Dipivefrin

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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