Combivent Clinical Pharmacology - ipratropium bromide and albuterol sulfate

[ipratropium bromide and albuterol sulfate]

CLINICAL PHARMACOLOGY

Combivent Inhalation Aerosol is a combination of the anticholinergic bronchodilator, ipratropium bromide, and the beta 2 -adrenergic bronchodilator, albuterol sulfate.

Ipratropium Bromide:

Mechanism of Action

Ipratropium bromide is an anticholinergic (parasympatholytic) agent which, based on animal studies, appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve. Anticholinergics prevent the increases in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) which are caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle.

Pharmacokinetics

The bronchodilation following inhalation of ipratropium bromide is primarily a local, site-specific effect, not a systemic one. Much of an administered dose is swallowed as shown by fecal excretion studies. Ipratropium bromide is a quaternary amine. It is not readily absorbed into the systemic circulation either from the surface of the lung or from the gastrointestinal tract as confirmed by blood level and renal excretion studies. Plasma levels of ipratropium bromide were below the assay sensitivity limit of 100 pg/ mL.

The half-life of elimination is about 2 hours after inhalation or intravenous administration. Ipratropium bromide is minimally bound (0 to 9% in vitro) to plasma albumin and 1-acid glycoprotein. It is partially metabolized to inactive ester hydrolysis products. Following intravenous administration, approximately one-half of the dose is excreted unchanged in the urine. Studies in rats have shown that ipratropium bromide does not penetrate the blood-brain barrier.

The pharmacokinetics of Combivent Inhalation Aerosol or ipratropium bromide have not been studied in patients with hepatic or renal insufficiency or in the elderly (See PRECAUTIONS).

Controlled clinical studies have demonstrated that ipratropium bromide does not alter either mucociliary clearance or the volume or viscosity of respiratory secretions. In studies without a positive control, ipratropium bromide did not alter pupil size, accommodation or visual acuity (See ADVERSE REACTIONS).