Olopatadine dramatically lowers the upregulation of ICAM (intercellular adhesion molecule)-1 in vitro induced by mast cell supernatant and suppresses the production of TNF-α from human conjunctival mast cells when exposed to anti-IgE antibodies [2].

Absorption, Distribution and Excretion
In healthy subjects, after ocular administration of olopatadine, the peak plasma concentration (Cmax) was 1.6 ± 0.9 ng/mL, reached approximately 2.0 hours later. The AUC was 9.7 ± 4.4 ng·h/mL. The mean absolute bioavailability of olopatadine after intranasal administration was approximately 57%. In healthy subjects, after intranasal administration twice daily, the steady-state peak plasma concentration (Cmax) was 6.0 ± 8.99 ng/mL, reached between 30 minutes and 1 hour after administration. The mean AUC was 66.0 ± 26.8 ng·h/mL. In patients with seasonal allergic rhinitis, the steady-state peak plasma concentration (Cmax) was 23.3 ± 6.2 ng/mL, reached between 15 minutes and 2 hours after administration, with a mean AUC of 78.0 ± 13.9 ng·h/mL. Olopatadine is primarily excreted in the urine. Following oral administration, approximately 70% and 17% of the total dose are excreted in the urine and feces, respectively. In an open-label study involving healthy Chinese subjects, the mean apparent volume of distribution after oral administration of olopatadine was 133.83 L. In another open-label study involving healthy Chinese subjects, the mean apparent oral clearance (CL/F) after oral administration of olopatadine was 23.45 L/h. Metabolites/Metabolites Olopatadine is primarily metabolized in the liver, but to a limited extent. According to oral pharmacokinetic studies, at least six circulating metabolites exist in human plasma. Following topical ocular administration of olopatadine, it is metabolized to olopatadine N-oxide under the catalysis of flavin monooxygenases (FMOs) 1 and 3, and was detected in the plasma of half of the patients at a concentration less than 10% of the total plasma volume 4 hours after administration. Olopatadine monodemethyl (or N-demethyl olopatadine) is metabolized by CYP3A4 and can be detected at very low concentrations in vivo. Known metabolites of olopatadine include N-monodemethyl olopatadine. Both the monodemethyl metabolite and the N-oxide metabolite are detected at low concentrations in urine. Elimination route: Primarily excreted via the kidneys. Half-life: 3 hours. Following ocular administration, the elimination half-life of olopatadine is 3.4 ± 1.2 hours. Oral pharmacokinetic studies indicate an elimination half-life of 8 to 12 hours.

Toxicity Summary
Olopatadine is a selective histamine H1 receptor antagonist that binds to histamine H1 receptors. This blocks the action of endogenous histamine, thereby temporarily relieving histamine-induced adverse symptoms. Olopatadine has no effect on alpha-adrenergic receptors, dopamine receptors, or muscarinic type 1 and 2 receptors.

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Effects During Pregnancy and Lactation
◉ Use During Lactation
Due to limited absorption through the eyes, lopatadine is not expected to have any adverse effects on breastfed infants. To significantly reduce the amount of medication that enters breast milk after using eye drops, press the tear duct near the corner of the eye for at least 1 minute, then wipe away any excess medication with absorbent tissue.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Breastfeeding and Breast Milk
No published information found as of the revision date.

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Protein Binding
Approximately 55% of olopatadine binds to human serum proteins, with serum albumin being the primary binding protein.

[1]. Topical Olopatadine in the Treatment of Allergic Conjunctivitis: A Systematic Review and Meta-analysis. Ocul Immunol Inflamm. 2017 Oct;25(5):663-677.

[2]. Olopatadine: a drug for allergic conjunctivitis targeting the mast cell. Expert Opin Pharmacother. 2010 Apr;11(6):969-81.

Pharmacodynamics
Inflammatory responses induced by various stimuli are mediated by endogenous mediators and other pro-inflammatory factors. Histamine receptor activation and mast cell degranulation are the main mechanisms leading to inflammatory responses such as itchy eyes, congestion, conjunctival edema, eyelid swelling, and tearing in seasonal allergic conjunctivitis. Olopatadine is an anti-allergic molecule and mast cell stabilizer that inhibits type I immediate hypersensitivity reactions in vivo. Olopatadine alleviates allergic and inflammatory symptoms at various administration sites, including the eyes and nose, by blocking the action of histamine. It has shown antihistamine activity in isolated tissues, animal models, and humans. Olopatadine has also shown dose-dependent inhibition of histamine release from immune-stimulated rat basophilic leukemia cells and human conjunctival mast cells (in vitro experiments). Olopatadine has a relatively rapid onset of action and a long duration of action, exerting its antihistamine effect from 5 minutes to 24 hours after administration. Although olopatadine is a non-sedating antihistamine, drowsiness has been reported in some patients using nasal olopatadine in clinical trials. Transient blurred vision or other visual disturbances have been observed after ophthalmic administration. Olopatadine has negligible effects on alpha-adrenergic receptors, dopamine receptors, muscarinic receptors type 1 and 2, and serotonin receptors. No QT interval prolongation was observed after intranasal administration of olopatadine in clinical trials.

337.41222

337.167

113806-05-6

Olopatadine hydrochloride;140462-76-6;Olopatadine-d6;1231979-85-3

5281071

Typically exists as solid at room temperature

1.2±0.1 g/cm3

523.0±50.0 °C at 760 mmHg

248 °C

270.1±30.1 °C

0.0±1.4 mmHg at 25°C

1.641

3.14

1

4

5

25

488

0

CN(C)CC/C=C\1/C2=CC=CC=C2COC3=C1C=C(C=C3)CC(=O)O

JBIMVDZLSHOPLA-LSCVHKIXSA-N

InChI=1S/C21H23NO3/c1-22(2)11-5-8-18-17-7-4-3-6-16(17)14-25-20-10-9-15(12-19(18)20)13-21(23)24/h3-4,6-10,12H,5,11,13-14H2,1-2H3,(H,23,24)/b18-8-

2-[(11Z)-11-[3-(dimethylamino)propylidene]-6H-benzo[c][1]benzoxepin-2-yl]acetic acid

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.)