Salbutamol Other names: Albuterol Salbutamol

Salbutamol is a selective Beta-2-adrenergic agonist administered for the symptomatic relief of bronchospasm associated with chronic or acute asthma, bronchitis or other obstructive pulmonary diseases.

Salbutamol is a selective β₂-agonist providing short-acting (4-6 hour) bronchodilation with a fast onset (within 5 minutes) in reversible airways obstruction. Because of its relative specificity for β₂ receptors, salbutamol relaxes smooth muscle of the bronchi, uterus and vascular supply to the skeletal muscle, but generally has much less stimulant action on the heart than does isoproterenol which has powerful action on all beta receptors.

At therapeutic doses it acts on the β₂-adrenoceptors of bronchial muscle. With its fast onset of action, it is particularly suitable for the management and prevention of attack in asthma.

Salbutamol is readily absorbed from the gastrointestinal tract. Its effects occur within 15 minutes and last for about 14 hours. The peak plasma concentration of salbutamol and its metabolites is 5.1-11.7μg% at 2.5-3 hours after an oral dose of 4mg. Salbutamol does not cross the blood brain barrier to a significant extent, but it crosses the placental barrier. The drug is excreted in urine in about 24 hours, 50% of the drug being excreted within 4 hours.

Salbutamol administered intravenously has a half-life of 4 to 6 hours and is cleared partly renally, and partly by metabolism to the inactive 4'-O-sulfate (phenolic sulfate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. Most of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. Salbutamol is bound to plasma proteins to the extent of 10%.

After administration by the inhaled route between 10 and 20% of the dose reaches the lower airways. The remainder is retained in the delivery system or is deposited in the oropharynx from where it is swallowed.

The fraction deposited in the airways is absorbed into the pulmonary tissues and circulation, but is not metabolised by the lung. On reaching the systemic circulation it becomes accessible to hepatic metabolism and is excreted, primarily in the urine, as unchanged drug and as the phenolic sulfate.

The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulfate. Both unchanged drug and conjugate are excreted primarily in the urine.

In common with other potent selective β2-agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of fetuses were found to have cleft palate at 2.5mg/kg dose, 4 times the maximum human oral dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50mg/kg/day orally throughout pregnancy resulted in no significant fetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care. Reproductive studies in the rabbit at doses of 50mg/kg/day orally (i.e. much higher than the normal human dose) have shown fetuses with treatment related changes; these included open eyelids (ablepharia), secondary palate clefts (palatoschisis), changes in ossification of the frontal bones of the cranium (cranioschisis) and limb flexure.

In an oral fertility and general reproductive performance study in rats at doses of 2 and 50 mg/kg/day, with the exception of a reduction in number of weanlings surviving to day 21 post partum at 50 mg/kg/day, there were no adverse effects on fertility, embryofetal development, litter size, birth weight or growth rate.