Targeting Inhaled Therapy beyond the Lungs

Abstract

Pulmonary disease has been the primary target of inhaled therapeutics for over 50 years. During that period, increasing interest has arisen in the use of this route of administration to gain access to the systemic circulation for the treatment of a number of diseases beyond the airways. In order to effectively employ this route, the barriers to transport from the lungs following deposition of aerosols must be considered, including the nature of the disease (whether proximal, as in pulmonary hypertension, or distal, as in diabetes). Delivery to the systemic circulation begins with the efficiency of aerosol generation and subsequent deposition in the airways and proceeds to the influence of mechanisms of clearance, including absorption, metabolism, and mucociliary and cell-mediated transport, on the residence time of the drugs in the lungs. The nature of the drug (small or large molecules/low or high molecular weight), susceptibility to degradation and general physicochemical properties play a role in the chemistry of its formulation, physics of aerosol delivery and biology of disposition.

Simultaneous measurement of perillyl alcohol and its metabolite perillic acid in plasma and lung after inhalational administration in Wistar rats

“…28 It has been established that P450 enzymes in the liver perform stepwise oxidation of POH toward its metabolic end products perillyl aldehyde and PA. Certain cells are known to be highly metabolic, such as, for example, Clara cells in the airways.…”

“…Certain cells are known to be highly metabolic, such as, for example, Clara cells in the airways. 28 It has been established that P450 enzymes in the liver perform stepwise oxidation of POH toward its metabolic end products perillyl aldehyde and PA. It is conceivable that a similar process takes place in lung tissue, which would explain the rapid depletion of POH and corresponding accumulation of PA within the cells of the lung, since all the metabolic enzymes found in the liver are also present in the lung, although in lower amounts.…”

“…It is conceivable that a similar process takes place in lung tissue, which would explain the rapid depletion of POH and corresponding accumulation of PA within the cells of the lung, since all the metabolic enzymes found in the liver are also present in the lung, although in lower amounts. 28 An additional factor for the rapid turnover of POH would be found in its high lipophilicity, which supports quick absorption by lung tissue and near immediate processing by the available enzymes. In agreement, expeditious turnover of POH to PA has also been observed by others in rats, dogs and humans.…”

Knowledge, attitude, practices of inhalational therapy among nursing staff posted at tertiary care teaching hospital

“…Inhalational drug route is one of the fastest, non-invasive methods of medications designed for treatment of respiratory disorders. 2,3 Metered dose inhalers (MDIs), dry powder inhalers (DPIs) and nebulizer and are most commonly used devices for delivering inhalational therapy. 4 Bronchodilators are frequently used in patients receiving invasive mechanical ventilation and commonly delivered through the inhalation route.…”

Knowledge, Attitudes and Preferences Among Spanish Community Pharmacists Regarding Inhaled Therapy (The Optim Pharmacy Study)

“…Although inhaled therapy can be utilized in a variety of diseases [2], its main use is in obstructive respiratory diseases. Inhaled therapy is the recommended treatment of choice in the clinical guidelines for asthma [3,4] and chronic obstructive pulmonary disease (COPD) [5,6].…”