Ipratropium Bromide

Ipratropium bromide is a type of anticholinergic (SAMA: short-acting muscarinic antagonist) medication that opens up the medium and large airways in the lungs. It is used to treat the symptoms of chronic obstructive pulmonary disease and asthma. It is used as an inhaler or nebulizer. The onset of action is typically within 15 to 30 minutes and lasts for three to five hours.

Ipratropium bromide was patented in 1966 and approved for medical use in 1974. It is on the World Health Organization’s List of Essential Medicines, the most important medicines needed in a health system. Ipratropium is available as a generic medication. In 2020, it was the 312th most commonly prescribed medication in the United States, with more than 900 thousand prescriptions.

Structure:

Physicochemical Data:

IUPAC Name     [8-methyl-8-(1-methylethyl)- 8-azoniabicyclo[3.2.1] oct-3-yl] 3-hydroxy-2-phenyl-propanoate
CAS Number22254-24-6
Molecular FormulaC20H30BrNO3
Molecular Mass412.368 g·mol−1
Melting Point231°C
Density 

Pharmacokinetic Data:

AbsorptionIpratropium is a topically active but poorly absorbed agent.7 The lack of absorption potential in the mucosal surfaces is associated with the presence of a charge in the 5-valent nitrogen. The molecule itself presents a very large topic of effectiveness however, it does not produce detectable blood levels or systemic effects.

Serum levels of ipratropium after oral or inhaled administration are very low, corresponding to only 1-2% of the administered dose. These low levels peak after 1-2 hours and it presents a low bioavailability of 2%.
Volume of DistributionIpratropium has a volume of distributions of 4.6 L/kg and hence, it is known to be highly distributed in the tissues.
Protein BindingThe protein binding of ipratropium is very low as the level of circulating ipratropium is very minimal. The bound state represents only 0-9% of the administered dose.
MetabolismIpratropium is metabolized in the gastrointestinal tract by the activity of the cytochrome P-450 isoenzymes. From the orally administered dose, about 90% of the dose is excreted unchanged. The absorbed portion is partially metabolized by ester hydrolysis to inactive metabolites, tropic acid, and tropane.
Route of EliminationAbout 80-100% of the administered dose of ipratropium is excreted in the urine leaving less than 20% of the dose to be eliminated through the feces. From the urine-eliminated portion, almost all the drug is found unchanged.

However, when ipratropium is orally administered, due to its low absorption, most of the dose is recovered in the feces with a very minimal amount found in the urine.
Half-lifeIpratropium presents a short half-life of about 1.6 hours.
ClearanceThe average clearance rate of ipratropium is 2.3 L/min with a renal clearance of 0.9 L/min.
ToxicityThe reported LD50 in mice after oral administration of ipratropium is 1500 mg/kg. However, overdosage is not very likely due to the poor absorption of ipratropium.

Ipratropium was not shown to present carcinogenesis, teratogenesis not mutagenesis potential and it did not present effects on fertility. The only effect after high administration of ipratropium was a reduction in the conception rate.

References:

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