Relationship Between Drug Delivery and Effect

To date there has been relatively little work correlating the pattern of deposition with the therapentic outcome or pharmacodynamic effects (118,124, 133-135). This perhaps is not too surprising, as most p-agonists are administered at or close to supramaximal doses and therefore generally administered close to the plateau of the dose response curve, while the therapeutic effects of inhaled steroids are observed over weeks and indeed for bronchial hypersre-sponsiveness further benefits are still being observed after a couple of years of therapy. 

Aerosol therapy has, to date, been used almost exclusively to treat pulmonary disease, but the era of using the respiratory tract to deliver potent systemic drugs and novel agents for pulmonary disease is dawning. 

Most drug delivery systems currently used to treat pulmonary disease were developed and introduced into clinical practice long before assessments of pulmonary drug delivery were undertaken. The pharmaceutical companies have seen little reason to improve on the current devices, utilizing technology that is many decades old, because the current systems do produce useful therapeutic responses and are relatively safe ( therapeutic index ) if used effectively. 

Measuring deposition under controlled conditions will provide an upper limit of deposition from that particular delivery device in the population studied. 

Studies have indicated that, even in tightly controlled settings, current systems are highly operator-dependent, and that it is not possible to predict pulmonary doses in cliifical practice. Pharmaceutical companies—and, perhaps more importantly, regulatory authorities— have not addressed this issue of operator dependence and intrasubject variability. The advent of novel delivery systems that do address these issues will force the pharmaceutical companies and regulators to consider these issues in some detail in the future. 

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