OXIS Inhalation powder Ref.[27705] Active ingredients: Eformoterol

Absorption

Inhaled formoterol is rapidly absorbed. Peak plasma concentration is reached about 10 minutes after inhalation.

In a pharmacokinetic study, the mean lung deposition of formoterol after inhalation via Turbohaler was 43% of the delivered dose. The total systemic availability was around 60% of the delivered dose.

Distribution and biotransformation

Plasma protein binding is approximately 50%.

Formoterol is metabolised via direct glucuronidation and O-demethylation. The enzyme responsible for O-demethylation has not been identified.

Elimination

The major part of the dose of formoterol is eliminated via metabolism. Total plasma clearance and volume of distribution has not been determined. After inhalation 8-13% of the delivered dose of formoterol is excreted unmetabolised in the urine. About 20% of an intravenous dose is excreted unchanged in the urine. The terminal half-life after inhalation is estimated to be 17 hours.

Linearity/non-linearity

Systemic exposure for formoterol correlates in a linear fashion to administered dose.

Special populations

The effect of decreased liver or kidney function on the pharmacokinetics of formoterol and the pharmacokinetics in the elderly is not known. As formoterol is primarily eliminated via liver metabolism an increased exposure can be expected in patients with severe liver cirrhosis.

The effects of formoterol seen in toxicity studies in rats and dogs were mainly on the cardiovascular system and consisted of hyperaemia, tachycardia, arrhythmias and myocardial lesions. These effects are known pharmacological manifestations seen after the administration of high doses of β₂-agonists.

No genotoxic effects of formoterol have been observed in in-vitro or in vivo tests. In rats and mice a slight increase in the incidence of benign uterine leiomyomas has been observed. This effect is looked upon as a class-effect observed in rodents after long exposure to high doses of β₂-agonists.