Clinical Pharmacology – Chemical
A finding of bioequivalence (BE) can shorten inhaler development, facilitate changes in product design during life-cycle changes and offer a way of introducing cheaper generic drug inhalers at end-of-patent life. Because most inhalers and aerosol drugs act topically however, tissue levels at the site of action do not necessarily relate to blood levels and, especially in the USA, pharmacokinetic comparisons between products are viewed largely as comparative “safety indicators”. On the other hand, existing pharmacodynamic techniques that seek to compare clinical effectiveness for topically acting drugs in their present doses, lack both the sensitivity and precision needed to be able to tell a significant difference between products. In vitro proof of BE is also a challenge. While existing conventional aerosol performance tests are sufficiently precise to distinguish between products in the laboratory, those methods fail to (a) predict drug aerosol deposition in different airway regions and (b) account for the variations in lung delivery efficiency offered by different inhaler platforms. Evolving approaches will be described that may overcome these problems by employing clinically relevant methods capable of comparing the total dose and the aerodynamic particle size distribution of orally inhaled drugs exiting geometrically realistic mouth-throat models under transient, but realistic, inhalation flow conditions.