ペミロラスト

In water, 1.9X10+4 mg/L at 25 °C /Estimated/

4.62e-01 g/L

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/

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/

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 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.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pemirolast potassium was not teratogenic in rabbits given oral doses up to 150 mg/kg ... /Pemirolast potassium/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pemirolast potassium caused an increased incidence of thymic remnant in the neck, interventricular septal defect, fetuses with wavy rib, splitting of thoracic vertebral body, and reduced numbers of ossified sternebrae, sacral and caudal vertebrae, and metatarsi when rats were given oral doses >/= 250 mg/kg during organogenesis. Increased incidence of dilation of renal pelvis/ureter in the fetuses and neonates was also noted when rats were given an oral dose of 400 mg/kg pemirolast potassium. /Pemirolast potassium/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pemirolast potassium produced increased pre- and post-implantation losses, reduced embryo/fetal and neonatal survival, decreased neonatal body weight, and delayed neonatal development in rats receiving an oral dose at 400 mg/kg. Pemirolast potassium also caused a reduction in the number of corpus lutea, the number of implantations, and number of live fetuses in the F1 generation in rats when F0 dams were given oral doses >/= 250 mg/kg during late gestation and the lactation period. /Pemirolast potassium/

/GENOTOXICITY/ Pemirolast potassium was not mutagenic or clastogenic when tested in a series of bacterial and mammalian tests for gene mutation and chromosomal injury in vitro nor was it clastogenic when tested in vivo in rats. /Pemirolast potassium/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pemirolast potassium had no effect on mating and fertility in rats at oral doses up to 250 mg/kg ... A reduced fertility and pregnancy index occurred in the F 1 generation when F 0 dams were treated with 400 mg/kg pemirolast potassium during late pregnancy and lactation period. /Pemirolast potassium/

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/

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 <i>in vivo</i> 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.

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/

4.5 hours (Ophthalmic)

...Mean half-life was 4.5 +/- 0.2 hours. /Pemirolast potassium/

2C09NV773M

PEMIROLAST

Physiologic Effects [PE] - Decreased Histamine Release

Established Pharmacologic Class [EPC] - Mast Cell Stabilizer

Pemirolast is a Mast Cell Stabilizer. The physiologic effect of pemirolast is by means of Decreased Histamine Release.

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/

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)