In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta₂-adrenergic receptors compared with isoproterenol. While it is recognized that beta₂-adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta₂-receptors in the human heart existing in a concentration between 10% and 50%. The precise function of these receptors has not been established (see WARNINGS).

The pharmacologic effects of beta-adrenergic agonist drugs, including albuterol, are at least in party attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic- 3¢, 5¢-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Albuterol has been shown in most controlled clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects.

Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes.

Albuterol is longer acting than isoproterenol in most patients by any route of administration because it is not a substrate for the cellular uptake processes for catecholamines nor for catechol-O-methyl transferase.

Additional Information for Inhalation Aerosol: The effects of rising doses of albuterol and isoproterenol aerosols were studied in volunteers and asthmatic patients. Results in normal volunteers indicated that albuterol is one half to one quarter as active as isoproterenol in producing increases in heart rate. In asthmatic patients similar cardiovascular differentiation between the two drugs was also seen.

Pharmacokinetics

Inhalation Aerosol and Capsules for Inhalation: Because of its gradual absorption from the bronchi, systemic levels of albuterol inhalation aerosol are low after inhalation of recommended doses. Studies undertaken with four subjects administered tritiated albuterol resulted in maximum plasma concentrations occurring within 2 to 4 hours. Due to the sensitivity of the assay method, the metabolic rate and half-life of elimination of albuterol in plasma could not be determined. However, urinary excretion provided data indicating that albuterol has an elimination half-life of 3.8 hours. Approximately 72% of the inhaled dose is excreted within 24 hours in the urine, and consists of 28% as unchanged drug and 44% as metabolite.

Inhalation Solution: Studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following either intermittent positive-pressure breathing (IPPB) or nebulizer administration; the remaining amount was recovered from the nebulizer and apparatus and expired air. Most of the absorbed dose was recovered in the urine 24 hours after drug administration. Following a 3-mg dose of nebulized albuterol in adults, the maximal albuterol plasma levels at 0.5 hours were 2.1 ng/ml (range, 1.4 to 3.2 ng/ml). There was a significant dose-related response in FEV₁ (forced expiratory volume in 1 second) and peak flow rate. It has been demonstrated that following oral administration of 4 mg of albuterol, the elimination half-life was 5 to 6 hours.

Bookmark this page: