H1 receptor (high affinity)
H2 receptor (high affinity)
H4 receptor (lower affinity) [1]

In guinea pig models, alcaftadine exhibited anti‑inflammatory activity in both acute and late‑phase allergic conjunctivitis.
In a murine model, a unique conjunctival epithelial stabilizing activity was observed with alcaftadine.
In human clinical trials using the conjunctival allergen challenge (CAC) model, alcaftadine 0.25% ophthalmic solution demonstrated superior efficacy compared to placebo in preventing ocular itching at 5 minutes post‑challenge (mean difference ≥1.92, p<0.001) and at 16 hours post‑instillation (mean difference ≥1.47). Onset of action was less than 15 minutes and duration of action exceeded 16 hours. [2]

Absorption, Distribution and Excretion
Based on data from oral acarboxylate administration, the carboxylate metabolite is primarily excreted unchanged in the urine. Metabolism/Metabolites The metabolism of acarboxylate is mediated by non-CYP450 cytoplasmic enzymes, producing the active carboxylate metabolite. Biological Half-Life Following topical ophthalmic application, the elimination half-life of the carboxylate metabolite is approximately 2 hours.

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Absorption: Following bilateral topical ocular administration, median time to maximum plasma concentration is 15 minutes for alcaftadine and 1 hour for its carboxylic acid metabolite.
Distribution: Protein binding is 39.2% for alcaftadine and 62.7% for the carboxylic acid metabolite.
Metabolism: Alcaftadine is metabolized by non‑CYP450 cytosolic enzymes to an active carboxylic acid metabolite.
Elimination: The half‑life of the carboxylic acid metabolite is approximately 2 hours.
Excretion: Following oral administration, alcaftadine is eliminated unchanged in the urine.
No systemic accumulation of alcaftadine or its metabolite occurs after daily topical ocular administration. Plasma concentrations fall below detectable limits for alcaftadine at 3 hours and for the metabolite at 12 hours after instillation. [2]

Protein Binding
The protein binding rates of acalovtidine and its active metabolite were 39.2% and 62.7%, respectively.

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Adverse effects: Incidence of ocular adverse effects is less than 4% and includes ocular irritation, pruritus, erythema, and stinging or burning upon instillation. These effects are typically mild and self‑limiting. Non‑ocular adverse effects include headache, nasopharyngitis, influenza, and dysgeusia.
Pediatric use: Efficacy data from children ≥10 years were extrapolated down to age 3 years; alcaftadine was safe and well tolerated in patients aged 3‑17 years. Not recommended for children <2 years.
Geriatric use: No clinically significant differences in adverse effect profile or efficacy in patients >64 years.
Pregnancy: Alcaftadine is pregnancy category B. In animal reproduction studies (rats, rabbits) with plasma exposure 200‑9000 times the expected human ocular dose, no evidence of impaired female reproduction or fetal harm was observed.
Drug interactions: No significant CYP enzyme interactions or alterations in serum protein binding have been identified. In vitro inhibition of alcaftadine metabolism (25‑33%) occurred with erythromycin, loratadine, and ketotifen at concentrations 5‑8 times therapeutic plasma levels. [2]

[1]. Namdar, R. and C. Valdez, Alcaftadine: a topical antihistamine for use in allergic conjunctivitis. Drugs Today (Barc), 2011. 47(12): p. 883-90.

[2]. Mahvan, T.D., W.A. Buckley, and J.R. Hornecker, Alcaftadine for the prevention of itching associated with allergic conjunctivitis. Ann Pharmacother, 2012. 46(7-8): p. 1025-32.

Alcaftadine is an imidazobenzozazepine compound with the chemical name 6,11-dihydro-5H-imidazo[2,1-b][3]benzozazepine, substituted with a formyl group at position 3 and a 1-methylpiperidin-4-yl group at position 11. It is an antihistamine used to treat allergic conjunctivitis. It acts as an H1 receptor antagonist and an anti-allergic agent. It is an aldehyde compound, belonging to the piperidine class of compounds, specifically the imidazobenzozazepine class, and is also a tertiary amine compound. Alcaftadine is an H1 histamine receptor antagonist, indicated for the prevention of itching caused by allergic conjunctivitis. It was approved for marketing in July 2010. Alcaftadine is a histamine-1 receptor antagonist. The mechanism of action of Alcaftadine is as a histamine H1 receptor antagonist.

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Drug Indications
For the prevention of itching caused by allergic conjunctivitis.
Indications
For the prevention of itching caused by allergic conjunctivitis.

FDA Label

Mechanism of Action

Acalatadine is an H1 histamine receptor antagonist that inhibits histamine release from mast cells. It has also been shown to reduce chemotaxis and inhibit eosinophil activation.
Pharmacodynamics

After topical administration of 0.25% acalatadine eye drops to both eyes, the mean peak plasma concentration (Cmax) of acalatadine is approximately 60 pg/mL, and the median time to peak concentration (Tmax) is 15 minutes. Three hours after administration, the plasma concentration of acalatadine is below the lower limit of quantitation (10 pg/mL). The mean Cmax of the active carboxylic acid metabolite is approximately 3 ng/mL, appearing 1 hour after administration. Twelve hours after administration, the plasma concentration of this carboxylic acid metabolite is below the lower limit of quantitation (100 pg/mL).

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Alcafadine is a topical antihistamine for use in allergic conjunctivitis. It is more effective than placebo and at least as effective as olopatadine 0.01% in preventing ocular itching at 15 minutes and at 16 hours after administration. The approved ophthalmic solution concentration is 0.025% for prevention of itching associated with allergic conjunctivitis in patients over 2 years of age. Comparative efficacy data of alcafadine to other ocular antihistamine/mast cell stabilizers are limited. [1]

C19H21N3O

307.3895

307.168

147084-10-4

19371515

Light yellow to yellow solid powder

1.2±0.1 g/cm3

556.2±60.0 °C at 760 mmHg

167 °C

290.2±32.9 °C

0.0±1.5 mmHg at 25°C

1.663

3.2

0

3

1

23

479

0

CN1CCC(=C2C3=CC=CC=C3CCN4C2=NC=C4C=O)CC1

MWTBKTRZPHJQLH-UHFFFAOYSA-N

InChI=1S/C19H21N3O/c1-21-9-6-15(7-10-21)18-17-5-3-2-4-14(17)8-11-22-16(13-23)12-20-19(18)22/h2-5,12-13H,6-11H2,1H3

2-(1-Methylpiperidin-4-ylidene)-4,7-diazatricyclo[8.4.0.0(3,7)]tetradeca- 1(14),3,5,10,12-pentaene-6-carbaldehyde

R-89674; R 89674; R89674; Alcaftadine; trade name: Lastacaft;

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)

DMSO : ≥ 40 mg/mL (~130.13 mM)

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.)