Bioequivalence of inhaled drugs.

Correspondence: E. Derom, Dept of Respiratory Diseases, University Hospital, De Pintelaan 185, B-9000 Gent, Belgium. It is generally accepted that inhalation therapy is the most effective way to treat patients with asthma or chronic obstructive pulmonary disease (COPD). Indeed, inhalation of relatively small doses of drug not only results in high, local concentrations in the airways the site of the disease but minimizes the risk for side-effects by decreasing the amount of drug reaching the systemic circulation. For more than 30 yrs, chlorofluorocarbondriven metered-dose inhalers have been considered as the device of choice for delivery of aerosolized drugs. They have been used in the numerous clinical trials which have been conducted over the last two decades in order to establish the appropriate dose regimens of inhaled β2-agonists, anticholinergics or corticosteroids in patients with mild, moderate, or severe asthma or COPD [1]. Two events have recently contributed to the development of alternative inhalation devices: the requirements to substitute chlorofluorocarbon (CFC) propellants with suitable alternatives [2]; and the expiry of patent for a number of inhaled medications, such as salbutamol and beclomethasone. In this context, generic CFC inhalers and new delivery systems, such as dry powder or CFCfree, pressurized inhalers, have been introduced or are currently under development. For many years, standardized methods have been used to demonstrate bioequivalence of orally or parenterally administered drugs. In contrast, generally-accepted, standardized guidelines to establish the bioequivalence of inhaled drugs were not available. New methods to compare bioequivalence from metered-dose inhalers are now being developed in the light of requirements of public health authorities concerning the rapidly increasing number of inhalation devices. The usefulness of such methods is illustrated in the study by MILLER and BRIGHT [3], published in the present issue of the European Respiratory Journal. Their study reveals a 36% difference in output between three generic inhalers, currently available in the UK, if used in conjunction with a large volume spacer.