Mechanism of action of bambuterol: a beta-agonist prodrug with sustained lung affinity

This paper reviews some characteristics of bambuterol; the bis-dimethylcarbamate prodrug of the bronchodilator terbutaline, especially its unique lung distribution properties following oral intake. Thus, animal studies, in vivo, show a high distribution of bambuterol to the lung, and an intermediate uptake of its metabolites, whereas the distribution to other tissues such as skeletal muscle, the myocardium, and the brain are negligible. Bambuterol is also metabolized in lung tissue, as shown by studies with the isolated, perfused guinea-pig lung. Moreover, some of the intermediate metabolites of bambuterol, formed mainly by oxidative metabolic processes in the liver, are chemically unstable, and may decompose spontaneously to the active drug, terbutaline, after lung uptake. Furthermore, the slow metabolism of bambuterol to terbutaline contributes strongly to its 24 hours duration of action. Some indirect evidence for the lung-specific distribution of bambuterol-generated terbutaline in asthmatic patients is also presented.