Pemirox

Pemirolast potassium.

See Table 1.

Click on icon to see table/diagram/image

Physicochemistry: Pemirolast potassium occurs as a light yellow crystalline powder. It is freely soluble in water, slightly soluble in methanol, and very slightly soluble in ethanol (99.5). It dissolves in potassium hydroxide TS.
Nonproprietary name: Pemirolast potassium.
Chemical name: Monopotassium 5-(9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-tetrazol-1-ide.
Molecular formula: C₁₀H₇KN₆O.
Molecular weight: 266.30.
Melting point: About 322°C (with decomposition).

Pharmacology: Inhibitory effect on experimental allergic conjunctivitis (rats and guinea pigs): In rats, intravenous or topical administration of pemirolast potassium demonstrated a strong inhibitory effect on vascular permeability increase in conjunctiva by Type I allergic reaction. It also showed an inhibitory effect on migration of eosinophils and neutrophils to conjunctival tissues in guinea pigs.
Duration of action (rabbits): The results of the time-course change in inhibitory effect of pemirolast potassium on allergic conjunctivitis in passively sensitized rabbits showed that the maximum inhibitory effect (about 60% inhibition) was observed 2 hours after administration and significant effects (40-50% inhibition) lasted for 12 hours.
Mechanism of action (Inhibitory effect on release of chemical mediators) (in vitro): Pemirolast potassium suppressed release of chemical mediators by inhibiting phospholipid metabolism of peritoneal mast cell membrane in rats. It also suppressed antigen- or anti-IgE antibody-induced release of histamine and SRS-A from human lungs, human peripheral leukocytes and guinea pig lungs.
Clinical studies: The effectiveness rates of Pemirox ophthalmic solution in clinical trials including double-blind studies conducted on 513 patients with allergic conjunctivitis or spring catarrh are summarized as follows. (See Table 2.)

Click on icon to see table/diagram/image

Pharmacokinetics: Blood concentration: Single-day administration study: The following table describes C_max and T_max of pemirolast potassium after the topical application of 0.1% or 0.5% pemirolast potassium ophthalmic solution at a dose of 2 drops, 4 times a day to 5 healthy adult male volunteers. (See Table 3.)

Click on icon to see table/diagram/image

One-week administration study: Plasma levels were determined after instillation of 2 drops of 0.5% pemirolast potassium ophthalmic solution, 4 times a day for 7 days to the eye of 6 healthy adult male volunteers. The data showed a similar tendency between the plasma levels on Day 1 and Day 7, suggesting no accumulation by multiple application. The plasma concentration 35 hours after the final instillation was below the lower limit of quantification (1.0 ng/mL).
Metabolism and excretion: Single-day administration study: Urinary excretion levels of pemirolast potassium were determined after instillation of 2 drops of 0.1% or 0.5% pemirolast potassium ophthalmic solution, 4 times a day to 5 healthy adult male volunteers. The drug level detected in 24-hour urine was 52.4 ± 19.6 μg on the day of administration, and that on the day following administration was below the lower limit of quantification (1.0 ng/mL).
One-week administration study: In a one-week administration study, 0.5% pemirolast potassium ophthalmic solution was instilled 4 times a day for 7 days to 6 healthy adult male volunteers. Pemirolast potassium excretion levels in 24-hour urine determined on Days 1, 4 and 7 showed no special variation. The levels in 24-hour urine sample were 286.0 ± 54.0 μg on the day of the last instillation and 54.5 ± 8.6 μg on the day following the completion of administration, but that after 2 days was below the lower limit of quantification in all subjects except one.
Ocular distribution (rabbits): The concentrations of pemirolast in respective outer ocular tissues including the conjunctiva, cornea and anterior sclera were higher than those in inner ocular tissues following topical application of 50 μL of 0.1% pemirolast potassium ophthalmic solution to the eye of rabbits. The drug concentrations in the cornea and the anterior sclera were decreased over time except for the conjunctiva in which the concentration was kept high enough to exert adequate pharmacological effects even 24 hours after instillation. It reached the peaks in the aqueous humor, iris, ciliary body 30 minutes, and in the retina-choroid at 15 to 30 minutes after instillation, then decreased to a trace amount from 8 hours. The concentrations in the lens and the vitreous body were negligible. Small amount of pemirolast potassium was detected in plasma 15 minutes after instillation but decreased below the lower limit of quantification at 4 hours after administration.

Allergic conjunctivitis and spring catarrh.

Usually, instill 1 drop a time to the eye twice daily (morning and evening).

Use in Children: The safety of this drug in prematures, newborns, and infants has not been established. No clinical experience.

This product should be used in pregnant women or women who may possibly be pregnant only if the expected therapeutic benefits are judged to outweigh the possible risks associated with treatment. The safety of this product during pregnancy has not been established.

Upon approval: Adverse reactions to this drug were reported in 16 (2.50%) of 639 patients in total. The major adverse reactions were blepharitis in 4 patients (0.63%), eye irritation in 4 patients (0.63%) and conjunctival hyperaemia in 3 patients (0.47%).
At the time of the reexamination completion: Adverse reactions to this drug were reported in 43 (1.01%) of 4,255 patients in total evaluated in drug-use results surveys and special surveys (those on long-term use and spring catarrh) after launching the product. The major adverse reactions were eye irritation in 16 patients (0.38%), blepharitis in 9 patients (0.21%), eyelid itching in 5 patients (0.12%), eye discharge in 5 patients (0.12%) and conjunctival hyperaemia in 5 patients (0.12%). If any adverse reactions are observed, appropriate measures such as discontinuing administration should be taken. (See Table 4.)

Click on icon to see table/diagram/image

Route of administration: Ophthalmic use only.
At the time of administration: (1) Instruct the patient to immediately wipe off any excess solution around the eye.
(2) Instruct the patient to be careful not to touch the tip of the bottle to the eye directly in order to avoid the contamination of the drug.

Store below 30°C.

Ophthalmic Decongestants, Anesthetics, Anti-Inflammatories

S01GX - Other antiallergics ; Used as ophthalmologic antiallergics.

P₁S₁S₃