Pemirolast

228.21

228.21

2C09NV773M

DTXSID1048338

C66334

Crystals from dimethylformamide

87.1

0.36 /Estimated/

1.64 g/cm3

310-311 °C (decomp)

454.8ºC at 760 mmHg

228.9ºC

4.62e-01 g/L

3.3X10-6 mm Hg at 25 deg C /Estimated/

Henry's Law constant = 4.9X10-11 atm-cu m/mole at 25 °C /Estimated/

Hydroxyl radical reaction rate constant = 3.0X10-11 cu cm/molecule-sec at 25 °C /Estimated/|Mol wt 266.30. Yellowish-white crytsalline powder. Highly soluble in water /Potassium salt/

II

8

UN 1993 3/PG 2

3

R34:Causes burns.

16-26-36/37/39-37/39

C

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl pemirolast potassium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pemirolast Potassium/

The effect of a newly developed anti-allergic drug, pemirolast potassium (TBX), on the pharmacokinetics and metabolism of theophylline was investigated under steady-state conditions in seven healthy male volunteers. A sustained-release theophylline formulation (100 mg twice daily at 12 h intervals) was given as monotherapy and coadministered with TBX (10 mg twice daily at 12 h). Plasma concentration-time curves and the urinary excretion of theophylline and its major metabolites after administration of theophylline alone and after coadministration with TBX were compared. No significant adverse effects from this study were observed. There were no significant differences in the total body clearance, renal clearance and maximum concentration of theophylline between the two treatments, although coadministration of TBX significantly delayed the time to reach maximum concentration of theophylline. In the case of urinary excretion, no significant changes in the fraction of urinary excretion of theophylline and its metabolites were observed. These results indicate that TBX has little or no effect on the pharmacokinetics and metabolism of theophylline and suggest that TBX is safe for asthma patients receiving theophylline therapy for treatment of chronic obstructive airway diseases.

Pemirolast potassium is excreted in the milk of lactating rats at concentrations higher than those in plasma. It is not known whether pemirolast potassium is excreted in human milk. /Pemirolast potassium/

For the prevention of itching of the eyes caused by allergies such as hay fever, and allergic conjunctivitis|FDA Label

Antiallergic|Pemirolast ophthalmic solution is indicated for the prophylaxis of itching of the eye associated with allergic conjunctivitis. /Included in US product labeling/ /Pemirolast potassium/|The preventive effect of pemirolast against restenosis after coronary stent placement was evaluated. Eighty-four patients with 89 de novo lesions who underwent successful coronary stenting were assigned to the pemirolast group (40 patients, 45 lesions) and the control group (44 patients, 44 lesions). Administration of pemirolast (20 mg/day) was initiated from the next morning 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 > or = 50% at follow-up. Intravascular ultrasound study conducted at follow-up angiography was used to measure vessel cross-sectional area (CSA), stent CSA, lumen CSA, neointima CSA (stent CSA--lumen CSA), and percentage neointima CSA (neointima CSA/stent CSA x 100%) at the minimal lumen site. There were no significant differences in baseline characteristics between the two groups. Restenosis rate was significantly lower in the pemirolast group than in the control group (15.0% vs 34.1% of patients, 13.3% vs 34.1% of lesions, p < 0.05, respectively). The intravascular ultrasound study at follow-up (36 lesions in the pemirolast group, 33 in the control group) found no significant differences in vessel CSA and stent CSA between the two groups(17.3 +/- 2.2 vs 16.8 +/- 2.4 mm2, 8.6 +/- 1.9 vs 8.4 +/- 1.7 sq mm, respectively). However, lumen CSA was significantly larger in the pemirolast group than in the control group (5.5 +/- 1.3 vs 4.4 +/- 1.1 sq mm, p < 0.05). Moreover, neointima CSA and percentage neointima CSA were significantly smaller in the pemirolast group (3.1 +/- 1.1 vs 4.0 +/- 1.2 sq mm, p < 0.05 and 36.2 +/- 15.9% vs 47.4 +/- 15.6%, p < 0.01). /Pemirolast potassium/

Headaches, rhinitis, and cold/flu symptoms occurred in 10-25% of patients in clinical trials. ... Ocular burning/stinging, dry eye, foreign body sensation, and ocular discomfort, which occurre in 1-2% of patients, were the most common adverse ocular effects reported in clinical studies. /Pemirolast potassium/|FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./ /Pemirolast potassium/|Pemirolast potassium is excreted in the milk of lactating rats at concentrations higher than those in plasma. It is not known whether pemirolast potassium is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Alamast ophthalmic solution is administered to a nursing woman. /Pemirolast potassium/|The following ocular and non-ocular adverse reactions were reported at an incidence of less than 5%: Ocular: burning, dry eye, foreign body sensation, and ocular discomfort. Non-Ocular: allergy, back pain, bronchitis, cough, dysmenorrhea, fever, sinusitis, and sneezing/nasal congestion. /Pemirolast potassium/|The preservative in ALAMAST, lauralkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red should be instructed to wait at least ten minutes after instilling ALAMAST before they insert their contact lenses. /Pemirolast potassium/

Pemirolast is used for the prophylactic treatment of itching of the eye associated with allergic conjunctivitis. Pemirolast potassium is a mast cell stabilizer that inhibits the in vivo Type I immediate hypersensitivity reaction. Pemirolast inhibits the antigen-induced release of inflammatory mediators (e.g., histamine, leukotriene C4, D4, E4) from human mast cells. Allergic reactions lead to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H₁-receptors, produces pruritis and vasodilatation (allowing blood fluids to enter the area to cause swelling). Pemirolast is a histamine H1 antagonist. It competes with histamine for the normal H₁-receptor sites on effector cells of blood vessels to provide effective, temporary relief of watery and itchy eyes.

Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only. (See all compounds classified as Histamine Antagonists.)

Following topical administration, about 10-15% of the dose was excreted unchanged in the urine.|A mean peak plasma level of 4.7 ng/mL occurred after 2 weeks of administration. /Pemirolast potassium/|Elimination: Renal, 84 to 90% of dose eliminated within 24 hours, about 10 to 15% of the dose was excreted unchanged. /Pemirolast potassium/|Pemirolast potassium is excreted in the milk of lactating rats at concentrations higher than those in plasma. It is not known whether pemirolast potassium is excreted in human milk.|Topical ocular administration of one to two drops of Alamast ophthalmic solution in each eye four times daily in 16 healthy volunteers for two weeks resulted in detectable concentrations in the plasma. The mean (+/- SE) peak plasma level of 4.7 +/- 0.8 ng/mL occurred at 0.42 +/- 0.05 hours and the mean half-life was 4.5 +/- 0.2 hours. /Pemirolast potassium/

Hepatic (Ophthalmic)

4.5 hours (Ophthalmic)|...Mean half-life was 4.5 +/- 0.2 hours. /Pemirolast potassium/

Pemirolast binds to the histamine H₁ receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Pemirolast has also been observed to inhibit antigen-stimulated calcium ion influx into mast cells through the blockage of calcium channels. Pemirolast inhibits the chemotaxis of eosinophils into ocular tissue, and prevents inflammatory mediator release from human eosinophils.|To determine whether pemirolast, a new antiallergic drug, inhibits the activation of eosinophils, we investigated the effect of pemirolast on the release of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP) from human eosinophils. Calcium ionophore A23187 caused both LTC4 and ECP release from human eosinophils, whereas PAF and FMLP induced only ECP release from the eosinophils. Pemirolast (10(-6) to 10(-3) M) inhibited A23187-induced LTC4 release from the eosinophils in a dose-dependent fashion with 77% inhibition at 10(-3) M. Pemirolast (10(-5) to 10(-3) M) inhibited A23187-induced ECP release from the eosinophils in a dose-dependent fashion with 42% inhibition at 10(-3) M. Pemirolast (10(-4) and 10(-3) M) also inhibited PAF-induced and FMLP-induced ECP release from the eosinophils. We conclude that pemirolast prevents the activation of human eosinophils to inhibit LTC4 and ECP release. These results suggest that pemirolast might be useful in controlling allergic diseases by inhibiting eosinophil activation. /Pemirolast potassium/|Pemirolast is a mast cell stabilizer and inhibits the release of inflammatory mediators from cells associated with Type I immediate hypersensitivity reactions. The drug has been observed to block antigen-stimulated calcium ion influx into mast cells. Pemirolast also inhibits the chemotaxis of eosinophils into ocular tissue, and prevents inflammatory mediator release from human eosinophils. /Pemirolast potassium/

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

Ophthalmic: Solution 0.1% Alamast (with lauralkonium chloride), (Santen)

Preparation: P.F. Juby, US 4122274 (1978 to Bristol-Myers)|Information available in 2004 indicated that Pemirolast potassium was used in the manufacture of pharmaceutical preparations in the following countries: Japan, USA (1,2)