Pharmacotherapeutic group: selective β2-agonists, bambuterol. ATC code: R03C C12.
Pharmacology: Pharmacodynamics: Bambuterol hydrochloride (BAMBEC) contains bambuterol, a prodrug of the adrenergic beta-receptor agonist terbutaline, which predominantly stimulates β2-receptors, thus producing relaxation of bronchial smooth muscle, inhibition of the release of endogenous spasmogens, inhibition of oedema caused by endogenous mediators and increased mucociliary clearance.
Pharmacokinetics: About 20% of an oral dose of bambuterol is absorbed. The absorption is not influenced by concomitant intake of food. After absorption, bambuterol is slowly metabolized via hydrolysis (plasma cholinesterase) and oxidation to active terbutaline. About 1/3 of the absorbed dose of bambuterol is metabolized in the intestinal wall and in the liver, mainly to intermediary metabolites.
Of the administered dose of bambuterol, about 10% is converted to terbutaline in adults. Children have a reduced clearance of terbutaline, but they also generate less terbutaline than adults. Therefore children aged 6-12 years should be given adult doses, whereas smaller children (2-5 years) usually need less.
Maximum plasma concentration of the active metabolite terbutaline is achieved within 2-6 hours. The effect-duration is at least 24 hours. Steady-state is reached after 4-5 days of treatment. The plasma half-life of bambuterol after oral administration is about 13 h. The plasma half-life of the active generated metabolite terbutaline is about 21 h.
Bambuterol and its metabolites, including terbutaline, are mainly excreted via the kidneys.
Toxicology: Preclinical safety data: The acute toxicity of bambuterol has been evaluated in studies in mice and rats and is rated as moderate. Repeated dose toxicity studies (1-12 months) in dogs revealed hyperemia, tachycardia and myocardial lesions, observations consistent with the known effects of beta-agonists.
In a 24-month carcinogenicity study in rats, a slightly increased incidence of thyroid follicular adenomas was noted at a dose of bambuterol that was more than 500 times the daily dose in humans. At doses about 150 times the clinical dose no such effect was found. The mechanism of development of thyroid adenomas in rats is considered to be a result of increased secretion of thyroid-stimulating hormone, induced by increased clearance of thyroxine. Such effects have previously been reported for a number of currently marketed drugs.