Source: Annual Congress 2006 - COPD and inflammation
Disease area: Airway diseases

Abstract

Background: Bimosiamose is a pan-selectin antagonist targeted against the three cell adhesion molecules E-, L- and P-selectin. It is currently in clinical development for the treatment of acute and chronic inflammatory lung disorders like ALI/ARDS, asthma or COPD. Desired route of administration is inhalation to limit the distribution of Bimosiamose to the alveolar space of the lung, thus avoiding systemic bioavailability.
Aim: The aim was to investigate tolerability and pharmacokinetics of Bimosiamose in the lung after inhalation.
Methods: Two different randomized, double-blind, placebo controlled phase I trials have been performed in healthy male subjects. In the dose escalating study subjects received single doses of 2 - 140 mg bimosiamose by inhalation via nebulizer, in the multiple dose study subjects received between 8 and 70 mg bimosiamose bid. For both studies 4 ml of a solution containing the test drug was administered via nebulizer over 15 minutes.
Results and Conclusions: Inhalation of bimosiamose was safe and well tolerated up to doses of 70 mg in both studies. After inhalation, Bimosiamose was detected in peripheral blood at and above 70 mg bid as well as 105 mg od. The highest plasma concentration of 64 ng/ml has been found after multiple inhalation of 70 mg bid. A relatively stable steady state plasma concentration Ctrough was achieved by inhalations bid whereas peak/ trough concentration ratio was quite small. The small Cmax/dose ratio suggested a very low level of systemic absorption and a high local concentration of Bimosiamose in the lung inhalation of Bimosiamose via nebulizer.

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M. Meyer, K. M. Beeh, J. Beier, E. Aydt, R. Zahlten, B. Jilma, G. Wolff (Berlin, Wiesbaden, Germany; Vienna, Austria). Tolerability and pharmacokinetics of inhaled bimosiamose in healthy human volunteers. Eur Respir J 2006; 28: Suppl. 50, 1995

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