Bambuterol

Bambuterol is an active precursor of the selective β₂-adrenergic agonist terbutaline. Bambuterol is the bisdimethylcarbamate of terbutaline, and is present in the formulation as a 1:1 racemate.

Pharmacodynamic effects

Pharmacodynamic studies have shown that after oral administration of bambuterol to guinea pigs, a sustained protective effect was achieved against histamine-induced bronchoconstriction. At equipotent doses, the duration of the relaxing activity was more prolonged than after plain terbutaline. Bambuterol, or the monocarbamate ester, did not exert any smooth muscle relaxing properties. The bronchoprotective effects seen after oral administration of bambuterol are related to the generation of terbutaline, as were the secondary effects (effects on other organs).

Pharmacodynamic studies have been conducted in asthmatics and healthy volunteers. The effects observed were bronchodilation, tremor and increases in heart rate. The metabolic effects included a small increase in blood glucose, while the effect on serum potassium was negligible. In short-term studies on lipoprotein metabolism, an increase in HDL cholesterol has been observed. In conclusion, all pharmacodynamic effects observed can be ascribed to the active metabolite terbutaline.

Absorption

On average, 17.5% of an oral dose is absorbed. Approximately 70–90% of the absorption occurs in the first 24 hours.

Biotransformation

Bambuterol is metabolised in the liver and terbutaline is formed by both hydrolysis and oxidation. After absorption from the gut, about ⅔ of terbutaline is first-pass metabolised, bambuterol escapes this first-pass metabolism. Of the absorbed amount, about 65% reaches the circulation. Bambuterol therefore has a bioavailability of about 10%.

Distribution

Protein binding of bambuterol is low, 40–50% at therapeutic concentrations.

Elimination

The terminal half-life of bambuterol after an oral dose is 9–17 hours.

Hepatic Impairment

All categories of subjects studied were able to form terbutaline in a predictive way except for liver cirrhotics.

Bambuterol has not revealed any adverse effects which pose a risk to man at therapeutic dosages in the toxicity studies.

Bambuterol is given as a racemate: (-)bambuterol is responsible for the pharmacodynamic effects via generation of ()- terbutaline. ()-bambuterol generates the pharmacodynamic inactive ()terbutaline. Both (+) and ()-bambuterol are equally active as plasma cholinesterase inhibitors. This inhibition is reversible.

The toxicity studies showed that bambuterol has β₂-stimulatory effects, expressed as cardiotoxicity in dogs, and at high doses, observed in the acute toxicity studies, cholinergic effects.

There is no evidence from the preclinical safety data to indicate that bambuterol cannot be used in man for the intended indications with sufficient safety.