Description
Proasma is a non-bronchodilator anti-asthmatic drug with marked antianaphylactic properties and a specific antihistaminic affect.
Laboratory experiments, both in vitro and in vivo, have revealed the following properties of Proasma, which may contribute to its anti- asthmatic activity.
- Inhibition, both of the acute bronchoconstrictor response, to PAF (Platelet Activating Factor) and of PAF-induced airway hyperresponsiveness.
- Inhibition of PAF-induced accumulation of eosinophils in the airways.
- Inhibition of the release of such chemical mediators as histamine and leukotrienes.
- Antagonism of acute bronchoconstriction due to leukotrienes.
- Reversal and prevention of experimentally-induced tachyphylaxis to isoprenaline.
In addition, Proasma exerts a powerful and sustained H1-receptor blocking activity which can be clearly dissociated from its anti- anaphylactic properties.
Pharmacokinetics
After oral administration the absorption of Proasma is nearly complete. Bioavailability amounts to approx. 50% due to a first pass effect of about 50% in the liver. Maximal plasma concentrations are reached within 2-4 hours. Protein binding is 75%. Ketotifen is eliminated biphasically with a short half-life of 3-5 hours and a longer one of 21 hours. In urine about 1% of the substance is excreted unchanged within 48 hours and 60-70% as metabolites. The main metabolite in the urine is practically inactive ketotifen-N- glucuronide.
The pattern of metabolism jn children is the same as in adults, but the clearance js higher in children.
Therefore, children above the age of 3 years require the same daily dosage regimen as adults. From the kinetic data, it is recommended that in children aged from 6 months to 3 years, half of the adult dose be administered.
