Salbutamol: how does it enter smooth muscle cells?

Polyspecific organic cation transporters (OCTs) in human cell membranes are involved in the uptake, distribution and excretion of cationic compounds. Although their relevance to drug disposition in the liver, small intestine and kidney has been investigated previously, less is known about the influence of these transporters on the pharmacokinetics and pharmacodynamics of inhaled drugs. Drugs that are commonly administered by inhalation for the treatment of respiratory diseases, such as glucocorticoids and cationic β(2)-agonists, might interact with several of these transporters, which are strongly expressed on the surfaces of airway epithelial cells. We evaluated the expression of OCT3 and measured the in vitro uptake of the short-acting β(2)-agonist salbutamol (SALB), alone or in combination with corticosterone (CS) and beclomethasone dipropionate (BDP), by bronchial smooth muscle cells. Our results showed that these cells express the OCT3 transporter and that SALB enters the cell in a transporter-independent fashion. Moreover, CS and BDP have different activities on SALB transport inside the cell. CS increases SALB transport and BDP decreases SALB transport, although neither of these effects are statistically significant. A better understanding of these mechanisms might lead to the improved treatment of airway diseases.