February 2002 / Volume 47 / Number 2 / Page 159
Dry Powder Ipratropium Bromide Is As Safe and Effective As Metered-Dose Inhaler Formulation: A Cumulative Dose-Response Study in Chronic Obstructive Pulmonary Disease Patients
Ipratropium bromide is a quaternary ammonium anticholinergic compound chemically related to atropine. Ipratropium bromide induces bronchodilation through a selective parasympathetic blockade of the bronchial muscarinic receptors. Since cholinergic tone substantially contributes to airway narrowing in patients with chronic obstructive pulmonary disease (COPD), ipratropium bromide is a mainstay in the management of those patients. The bronchodilator action of ipratropium bromide is dose-dependent, and the recommended dose is not a definite dose but rather a range of doses, depending on the subject, the disease, and the severity of the disease. Regular use of ipratropium bromide has been associated with improvement above baseline lung function and in acute response to bronchodilator therapy after 90 days. Long-term treatment with ipratropium bromide could be associated with improvement in dyspnea, especially in a subgroup of responder patients who show > or =15% increase in baseline forced expiratory volume in the first second (FEV1) after administration of 80 micrograms of ipratropium bromide.
Metered-dose inhalers (MDIs) have proven safe, effective, and convenient for delivering ipratropium bromide to COPD patients. However, several drawbacks encountered with MDIs have led to the development and testing of alternative devices such as dry powder inhalers (DPIs). DPIs do not require the coordination of actuation and inhalation that many patients are unable to perform with MDI. Moreover, DPIs use no propellants, such as chlorofluorocarbon (CFC), which contributes to depletion of the ozone layer in the stratosphere. The Montreal Protocol, which was adopted by several governments in 1987 and has been modified 5 times to date, aims to reduce and eventually eliminate emission of man-made ozone-depleting substances. In this context, DPI may be a suitable alternative for administering inhaled drugs. Recently a DPI that uses lactose as an excipient was designed for ipratropium bromide inhalation. Earlier powder inhalation formulations of ipratropium bromide used anhydrous glucose as the carrier substance, but the rate and extent of water uptake is less with lactose than with glucose, so the lactose-excipient DPI is less sensitive to environmental humidity than glucose-excipient DPI.
It is therefore important to study the efficacy of the lactose-excipient DPI and to compare its efficacy and safety profile to other established devices. The aim of the present study was to compare the safety and efficacy of ipratropium bromide in COPD patients when taken as an inhaled powder via the lactose-excipient DPI and as a pressurized aerosol via MDI. We used a cumulative dose-response model and also evaluated the tolerability and patient acceptance of the DPI.
The entire text of this article is available in the printed version of the February 2002 RESPIRATORY CARE.