TOXICOLOGIC TESTING OF INHALED PHARMACEUTICAL AEROSOLS

This paper reviews technical issues related to the toxicologic testing of inhaled pharmaceuticals. Although there are commonalities between approaches to general and inhalation toxicity testing, there also are specific challenges in the toxicity testing of inhaled pharmaceuticals . A major issue is that of dose; inhaled dose is more difficult to det ermine than intravenous or oral doses. Also, it is harder to relate do se in laboratory animals to that in man for inhalation exposure than f or other routes of administration. Additionally, in the case of inhale d pharmaceuticals, people generally inhale through the mouth, whereas most laboratory animals inhale primarily through the nose. This presen ts significant challenges in exposure methodology and technology that often need innovative approaches involving alteration to particle size of the agent or dosing procedure. Because the respiratory tract is th e site of deposition, local respiratory toxicity and possible damage t o lung cells need to be assessed. Systemic toxicity also needs to be e valuated and may be an issue in some cases. Special studies on pulmona ry function, mucociliary clearance, or immune response may be needed, depending on the nature of the inhaled pharmaceutical. This review exp lores the main issues involved in toxicity testing of inhaled pharmace uticals, the approaches that have been used, and the current and futur e challenges.