Saltropium Mechanism of Action

Pharmacology: Pharmacodynamics: Ipratropium bromide is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties.
In preclinical studies, it appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve. Anticholinergics prevent the increase in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) caused by the interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle.
The bronchodilation following inhalation of ipratropium bromide is primarily local and site-specific to the lung and not systemic in nature.
Salbutamol sulfate is a β2-adrenergic agent that acts on airway smooth muscle resulting in relaxation.
Salbutamol relaxes all smooth muscle from the trachea to the terminal bronchioles and protects against all bronchoconstrictor challenges.
Salbutamol + Ipratropium Bromide (Saltropium) provides the simultaneous release of ipratropium bromide and salbutamol sulfate allowing the additive effect on both muscarinic and β2-adrenergic receptors in the lung resulting in a bronchodilation which is superior to that provided by each single agent.
Controlled studies in patients with reversible bronchospasm have demonstrated that Salbutamol + Ipratropium Bromide (Saltropium) has a greater bronchodilator effect than either of its components and there was no potentiation of adverse events.
Pharmacokinetics: Ipratropium bromide is quickly absorbed after oral inhalation. The systemic bioavailability after inhalation is estimated to be <10% of the dose. Renal excretion of ipratropium bromide is given as 46% of the dose after IV administration. The half-life (t¹/₂) of the terminal elimination phase is about 1.6 hours as determined after IV administration.
The t¹/₂ for elimination of drug and metabolites is 3.6 hours, as determined after radiolabeling. Ipratropium bromide does not penetrate the blood-brain barrier.
Salbutamol sulfate is rapidly and completely absorbed following oral administration either by the inhaled or gastric route. Peak plasma salbutamol concentrations are seen within 3 hours of administration and are excreted unchanged in the urine after 24 hours. The elimination t¹/₂ is 4 hours.
Salbutamol will cross the blood-brain barrier reaching concentrations amounting to about 5% of the plasma concentrations.
It has been shown that co-nebulization of ipratropium bromide and salbutamol sulfate does not potentiate the systemic absorption of either component and that therefore, the additive activity of Salbutamol + Ipratropium Bromide (Saltropium) is due to the combined local effect on the lung following inhalation.