ABSTRACT
The US Food and Drug Administration (USFDA) defines bioavailability as “[t]he rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.” This definition cannot be generalized for all drugs administered by the pulmonary route, as some inhaled drugs do not require absorption to exert their actions, but others do. Thus, before calculating or interpreting the bioavailability of an inhaled compound, it is important to define the site of intended action. For example, the site of action for drugs intended to treat asthma is the airways, and these drugs do not require absorption into systemic circulation to exert their action. In contrast, the site of action for drugs intended to treat tuberculosis is the lungs and other organs in the body, and these drugs do need to be absorbed to exert their effect. Chapter 5 reviews the factors that influence the bioavailability of inhaled drugs and presents the methods preferred by the USFDA to determine bioavailability and bioequivalence. Case studies illustrating the preclinical and clinical determination of bioavailability and bioequivalency are presented for each site of action where absorption of the compound may or may not be required.
