Session Speaker

Application Of The New Emea Rules To Study Lung Deposition Ans Systemic Exposure Of Inhalers: An Evaluation In Three Antiasthmatic Drugs
L. Silvestro, Simona Rizea Savu, Silviu Savu, Adrian Ghita, Lina Remis
Germany

In the last EMEA rules (2009) on antiasthmatic inhalers (i.e. dry powder inhalers), the determination of plasma concentrations after administration with and without activated charcoal has been introduced as the main tool to evaluate their lung deposition and total systemic exposure.

We have performed clinical trials with 3 anti-asthmatic drugs this new approach. In addition to the EMEA guideline, an oral administration of the same products was done, in order to simulate 100 % ingestion by the gastro-enteric tract.

Based on the obtained data we can now state that activated charcoal permits to block efficiently the oral absorption of these drugs. On the other side, the oral administration arm let us observe that the three tested products have a quite different relative bioavailability, depending on their absorption characteristics, even more complicated by the fact that activated charcoal modifies the entero-hephatic recycling of the drugs excreted in the bile and also because of their peculiar metabolic processes.

We concluded that this approach to study lung deposition and total systemic exposure proved to be effective but additional experiments are recommended to better investigate the ingested versus the inhaled fraction, which is as much substance dependent as well as device dependant.