Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.

Afatinib displayed a complete mass balance with the main route of excretion via feces. Afatinib undergoes minimal metabolism.

Oral administration of Lefradafiban maintains the potent platelet GP IIb/IIIa antagonism of Fradafiban during treatment of healthy subjects for 1 week without signs of loss of the antiplatelet activity.

Hospitalisation, although it is believed to protect subjects from confounding environmental factors, can itself be associated with increases in liver enzyme levels. The definition of a relevant increase can be used to identify subjects who need further evaluation. The cause of the increase in liver enzyme levels remains unclear.

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