A23187-induced LTC4 and ECP release from eosinophils is dose-dependently inhibited by pemirolast (1 μM-1 mM) [1]. Pemirolast (0.1 mM and 1 mM) also prevents eosinophil ECP release that is triggered by FMLP and PAF [1]. By limiting human eosinophil activation, pirazolast reduces the production of granular proteins LTQ and ECP, which helps to alleviate and regulate allergic disorders [1]. Human conjunctival mast cells' histamine production is not substantially inhibited by pemirolast (100 nM-1 mM; 1–15 minutes) [2]. Pemirolast (0.1 μg/mL-0.01 mg/mL) suppresses the production of 1,2-diacylglycerol and the degranulation reaction of antigen and compound 48/80 in rat peritoneal mast cells, thereby inhibiting the signal transmission phospholipase C. and phosphatidyl acid and AZ activation [3].

Pemirolast blocks rats' release of sensory neuropeptides, which effectively reduces paclitaxel allergic reactions [4]. Half an hour after starting paclitaxel (15 mg/kg; i.v.) at a dose of 1 mg/kg, pemirolast (0.1-1 mg/kg; i.v.) inhibits and reverses the decrease in arterial PaO2 caused by paclitaxel-induced pulmonary vascular hyperpermeability. 4]. Thirty minutes after paclitaxel injection (15 mg/kg; iv), pemirolast (1 mg/kg; iv) reverses the increases in sensory neuropeptide (CGRP, substance P, and neurokinin A) concentrations caused by paclitaxel [4]. Pemirolast (10 mg/kg/d; oral; days 4-5) inhibits the release of substance P in rat cerebrospinal fluid (CSF) induced by cisplatin and significantly reduces kaolin intake on days 3 and 4[5].

Animal/Disease Models: Male Wistar rats (6 weeks old, 160-250 g) [5]
Doses: 10 mg/kg
Route of Administration: po (oral gavage); 5 days: 1 hour or 30 minutes before and after cisplatin administration
Experimental Results: Inhibition of cisplatin-induced increase in kaolin intake at 24, 48, 72 and 96 hrs (hrs (hours)) (5 times in total) (2-10 mg/kg; iv) on days 3 and 4 without reduction in normal feed intake .

---

Animal/Disease Models: Male Wistar rats (6 weeks old, 160-250 g) [5]
Doses: 10 mg/kg
Route of Administration: po (oral gavage); 4 days: 30 days before cisplatin (5 mg/kg; iv) administration minutes and 24, 48, 72 and 96 hrs (hrs (hours)) after dosing (four times in total).
Experimental Results: Significant reversal of cisplatin-induced elevation of substance P levels in cerebrospinal fluid to vehicle levels.

Absorption, Distribution and Excretion
Following topical application, approximately 10-15% of the dose is excreted unchanged in the urine. Two weeks after administration, the mean peak plasma concentration was 4.7 ng/mL. /Pemirost Potassium/
Elimination: Excreted by the kidneys; 84% to 90% of the dose is eliminated within 24 hours, and approximately 10% to 15% is excreted unchanged. /Pemirost Potassium/
Pemirost potassium concentrations in the milk of lactating rats are higher than plasma concentrations. It is unclear whether pemirost potassium is excreted into human milk.
In 16 healthy volunteers, 1-2 drops of Alamast eye drops were instilled into each eye four times daily for two weeks. Drug concentrations were detected in plasma. The mean (± standard error) peak plasma concentration was 4.7 ± 0.8 ng/mL, the time to occurrence was 0.42 ± 0.05 hours, and the mean half-life was 4.5 ± 0.2 hours. /Pemerost potassium/

---

Metabolism/Metabolites
Liver (Ophthalmic)

---

Biological half-life
4.5 hours (Ophthalmic)
...Mean half-life is 4.5 ± 0.2 hours. /Pemerost potassium/

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
While there are currently no published data on the use of pimiurolast during lactation, the drug concentration in breast milk is likely to be very low after the use of eye drops.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date. Drug Interactions This study investigated the effects of a newly developed antihistamine, pimiurolast potassium (TBX), on the pharmacokinetics and metabolism of theophylline in seven healthy male volunteers under steady-state conditions. Subjects received either monotherapy with a sustained-release theophylline formulation (100 mg twice daily, 12 hours apart) or in combination with TBX (10 mg twice daily, 12 hours apart). This study compared the plasma concentration-time curves and urinary excretion of theophylline and its major metabolites after administration of theophylline alone and in combination with TBX. No significant adverse reactions were observed. There were no significant differences in total clearance, renal clearance, and peak concentration of theophylline between the two treatment regimens, but the combination with TBX significantly delayed the time to peak concentration. Regarding urinary excretion, there were no significant changes in the urinary excretion fraction of theophylline and its metabolites. These results indicate that TBX has minimal or no effect on the pharmacokinetics and metabolism of theophylline, suggesting that TBX is safe for asthmatic patients receiving theophylline treatment for chronic obstructive airway disease.

[1]. Kawashima T, et al. Inhibitory effect of pemirolast, a novel antiallergic drug, on leukotriene C4 and granule protein release from human eosinophils. Int Arch Allergy Immunol. 1994;103(4):405-9.
[2]. Yanni JM, et al. Comparative effects of topical ocular anti-allergy drugs on human conjunctival mast cells. Ann Allergy Asthma Immunol. 1997 Dec;79(6):541-5.
[3]. Fujimiya H, et al. Effect of a novel antiallergic drug, pemirolast, on activation of rat peritoneal mast cells: inhibition of exocytotic response and membrane phospholipid turnover. Int Arch Allergy Appl Immunol. 1991;96(1):62-7.
[4]. Itoh Y, et al. Pemirolast potently attenuates paclitaxel hypersensitivity reactions through inhibition of the release of sensory neuropeptides in rats. Neuropharmacology. 2004 May;46(6):888-94.
[5]. Tatsushima Y, et al. Pemirolast reduces cisplatin-induced kaolin intake in rats. Eur J Pharmacol. 2011 Jul 1;661(1-3):57-62.

Pemirolast is a pyridopyrimidine compound. Pemirolast potassium is a pale yellow powder, soluble in water. It is a mast cell stabilizer with anti-allergic properties. Pemirolast is a sterile aqueous ophthalmic solution used to prevent allergic eye itching, such as hay fever and allergic conjunctivitis. Pemirolast may help prevent pulmonary allergic reactions caused by drugs such as paclitaxel. Pemirolast is a mast cell stabilizer. The physiological action of pemirolast is achieved by reducing histamine release. Pemirolast is a pyrimidinone derivative with anti-allergic activity. Pemirolast blocks antigen-mediated calcium ion inflow into mast cells. This prevents mast cell degranulation, thereby stabilizing mast cells and inhibiting the release of inflammatory mediators such as histamine and leukotrienes, which are involved in the allergic process. Pemirolast can also prevent eosinophils from releasing inflammatory mediators. Drug Indications For the prevention of itchy eyes caused by allergies, such as hay fever and allergic conjunctivitis. FDA Label Mechanism of Action Pemirolast binds to histamine H1 receptors. This blocks the effects of endogenous histamine, thus temporarily relieving histamine-induced adverse symptoms. Pemirolast has also been found to inhibit the influx of antigen-stimulated calcium ions into mast cells by blocking calcium channels. Pemirolast inhibits eosinophil chemotaxis to ocular tissues and prevents the release of inflammatory mediators from human eosinophils. To determine whether the novel anti-allergy drug pemirolast inhibits eosinophil activation, we investigated the effects of pemirolast on the release of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP) from human eosinophils. Calcium ionophore A23187 induces the release of LTC4 and ECP from human eosinophils, while platelet-activating factor (PAF) and FMLP only induce the release of ECP. Piperamifloxacin (10⁻⁶ to 10⁻³ M) inhibited A23187-induced eosinophil LTC4 release in a dose-dependent manner, with an inhibition rate of 77% at 10⁻³ M. Piperamifloxacin (10⁻⁵ to 10⁻³ M) inhibited A23187-induced eosinophil ECP release in a dose-dependent manner, with an inhibition rate of 42% at 10⁻³ M. Piperamifloxacin (10⁻⁴ and 10⁻³ M) also inhibited PAF- and FMLP-induced eosinophil ECP release. We conclude that piemirost inhibits the release of LTC4 and ECP by inhibiting the activation of human eosinophils. These results suggest that piemirost may be used to control allergic diseases by inhibiting eosinophil activation. /Pemirost Potassium/
Pemirost is a mast cell stabilizer that inhibits the release of inflammatory mediators associated with type I immediate hypersensitivity reactions. This drug has been observed to block the influx of antigen-stimulated calcium ions into mast cells. Pemirost also inhibits eosinophil chemotaxis to ocular tissues and prevents the release of inflammatory mediators from human eosinophils. /Pemirost Potassium/

---

Therapeutic Use
Antiallergic Drug
Pemirost eye drops are indicated for the prevention of itchy eyes caused by allergic conjunctivitis. /US Product Label Contains//Pemirost Potassium/
Pemirost has been evaluated for its preventive effect against restenosis following coronary artery stenting. Eighty-four patients with a total of 89 new lesions successfully underwent coronary artery stenting and were randomly assigned to two groups: the pamirolastate group (40 patients, 45 lesions) and the control group (44 patients, 44 lesions). Pamirolastate (20 mg/day) was started the day after stenting and continued for 6 months of follow-up. Quantitative coronary angiography was performed immediately after stenting and at follow-up. Angiographic restenosis was defined as diameter stenosis ≥50% at follow-up. Intravascular ultrasound was performed at follow-up angiography to measure the cross-sectional area of the vessel at the minimum lumen (CSA), stent CSA, lumen CSA, neointimal CSA (stent CSA - lumen CSA), and the percentage of neointimal CSA (neointimal CSA/stent CSA × 100%). There were no significant differences in baseline characteristics between the two groups. Compared with the control group, the restenosis rate was significantly lower in the pemirostim group (patient proportions were 15.0% and 34.1%, respectively; lesion proportions were 13.3% and 34.1%, respectively, p < 0.05). Intravascular ultrasound examination during follow-up (36 lesions in the pemirostim group and 33 lesions in the control group) showed no significant differences in vessel cross-sectional area (CSA) and stent cross-sectional area (SSA) between the two groups (17.3 ± 2.2 mm² and 16.8 ± 2.4 mm², 8.6 ± 1.9 mm² and 8.4 ± 1.7 mm², respectively). However, the luminal cross-sectional area in the pemirostim group was significantly larger than that in the control group (5.5 ± 1.3 mm² and 4.4 ± 1.1 mm², p < 0.05). Furthermore, in the pemilauside group, the cross-sectional area of neointima (CSA) and the percentage of neointima were significantly smaller than in the control group (3.1 ± 1.1 mm² vs 4.0 ± 1.2 mm², p < 0.05; 36.2 ± 15.9% vs 47.4 ± 15.6%, p < 0.01). /Pemilauside Potassium/

---

Drug Warnings
In clinical trials, headache, rhinitis, and cold/flu symptoms occurred in 10-25% of patients. …Burning/tingling sensation in the eyes, dry eye, foreign body sensation, and eye discomfort were the most common adverse ocular reactions reported in clinical studies, with an incidence of 1-2%. /Pemilauside Potassium/
FDA Pregnancy Risk Classification: C / Risk cannot be ruled out. There are currently insufficient and well-controlled human studies, and animal studies have not shown any risk to the fetus or lack relevant data. Use of this drug during pregnancy may cause harm to the fetus; however, the potential benefits may outweigh the potential risks. / /Pemirostar Potassium/
The concentration of pemirostar potassium in the milk of lactating rats is higher than that in plasma. It is unknown whether pemirostar potassium is excreted into human milk. Because many drugs are excreted into human milk, caution should be exercised when using ALAMAST eye drops during lactation. / /Pemirostar Potassium/
The following ocular and non-ocular adverse reactions occur in less than 5% of cases: Ocular: burning sensation, dry eye, foreign body sensation, and eye discomfort. Non-ocular: allergic reactions, back pain, bronchitis, cough, dysmenorrhea, fever, sinusitis, and sneezing/nasal congestion. / /Pemirostar Potassium/
The preservative ammonium lauroyl chloride in ALAMAST may be absorbed by soft contact lenses. Patients wearing soft contact lenses and whose eyes are not red should be advised to wait at least ten minutes after instilling ALAMAST before wearing their contact lenses. /Pemerostil Potassium/

---

Pharmacodynamics
Pemerostil is used for the prophylactic treatment of itchy eyes caused by allergic conjunctivitis. Pemerostil potassium is a mast cell stabilizer that inhibits type I immediate hypersensitivity reactions in the body. Pemerostil inhibits the release of inflammatory mediators (such as histamine, leukotrienes C4, D4, E4) from antigen-induced human mast cells. Allergic reactions lead to cell degranulation and the release of histamine (and other chemical mediators) from mast cells or basophils. After histamine release, it can react with local or systemic tissues via histamine receptors. Histamine acts on H1 receptors, causing itching and vasodilation (causing blood to flow into the area, resulting in swelling). Pimecrolimus is a histamine H1 receptor antagonist. It competes with histamine for normal H1 receptor sites on vascular effector cells, thereby effectively and temporarily relieving tearing and itching of the eyes.

C10H8N6O

228.21012

228.076

69372-19-6

Pemirolast potassium;100299-08-9

57697

Crystals from dimethylformamide

1.64 g/cm3

454.8ºC at 760 mmHg

310-311ºC (decomposes)

228.9ºC

0.183

1

5

1

17

489

0

CC1=CC=CN2C1=NC=C(C2=O)C3=NNN=N3

HIANJWSAHKJQTH-UHFFFAOYSA-N

InChI=1S/C10H8N6O/c1-6-3-2-4-16-9(6)11-5-7(10(16)17)8-12-14-15-13-8/h2-5H,1H3,(H,12,13,14,15)

9-methyl-3-(2H-tetrazol-5-yl)pyrido[1,2-a]pyrimidin-4-one

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 : ~100 mg/mL (~438.19 mM)
DMF :< 1 mg/mL

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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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