Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Other antihistamines for systemic use, ATC code: R06AX17 Pharmacodynamic effects
Profiten is a non-bronchodilator, anti-asthmatic drug which inhibits the effect of certain endogenous substances known to be inflammatory mediators, and thereby exerts anti-allergic activity.
Laboratory experiments indicate that this anti-anaphylactic activity may be due to the inhibition of release of allergic mediators such as histamine and leukotrienes. The suppression of the priming of eosinophils by human recombinant cytokines and thereby suppression of the influx of eosinophils into inflammatory loci and the inhibition of the development of airway hyperactivity associated with activation of platelets by PAF (platelet activating factor) or caused by neural activation following the use of sympathomimetic drugs or the exposure to allergen. In addition, Profiten exerts a non- competitive blocking effect on histamine (H1) receptors. Therefore, it can also be used in place of classical histamine (H1) receptor antagonists.
Profiten is an established product. There are no new clinical studies.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Absorption
After oral administration the absorption of Profiten is almost complete. Bioavailability amounts to approximately 50% owing to a first pass effect of about 50% in the liver. Maximal plasma concentrations are reached within 2-4 hours.

Distribution
Protein binding is 75%.

Biotransformation
The main metabolite is ketotifen-N-glucuronide. This is practically inactive.

Elimination
Ketotifen is eliminated biphasically with a short half-life of 3-5 hours and a longer one of 21 hours.
About 1% of the substance is excreted unchanged in the urine within 48 hours and 60-70% as metabolites.
Effect of food
The bioavailability of Profiten is not influenced by the intake of food. Therefore Profiten can be taken with or without food. However, smooth plasma concentration profile may be observed when administered with meals.

Special populations

Pediatrics
The pattern of metabolism in children is the same as in adults, but the clearance is higher in children below 3 years. Therefore, the ketotifen dose per kilogram is higher for children compared to the adults. Children over the age of 3 years therefore require the same daily dose regimen as adults.

Hepatic impairment
No relevant pharmacokinetic studies have been performed with Profiten in patients with hepatic impairment. Since ketotifen is metabolized in the liver and its glucuronidation may be impaired in severe hepatic impairment, the clearance of ketotifen will most likely be reduced in patients with severe hepatic impairment and the possibility of accumulation of unchanged drug cannot be excluded.

Renal impairment
No relevant pharmacokinetic studies have been performed with Profiten in patients with renal impairment. However, considering that 60-70% of the dose is excreted in urine as metabolites, an increased risk of adverse reactions due to accumulation of metabolites cannot be excluded.