Kinetics and distribution of the β-adrenergic agonist salbutamol in rat brain

the kinetics of the beta-adrenergic agonist salbutamol and its distribution in the central nervous system were examined in rats by high-performance liquid chromatography with electrochemical detection. After 10 mg kg-1 i.v. salbutamol, the decline in drug plasma concentrations was biphasic and salbutamol was cleared very rapidly with a beta-half-life of about 37 min. Salbutamol rapidly penetrated the 'blood-brain barrier' and reached brain concentrations amounting to about 5% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands) the drug achieved concentrations more than 100 times those in whole brain. The results support the hypothesis that stimulation of central beta-adrenergic sites is responsible for salbutamol's pharmacological and biochemical effects.