Bile acid conjugates to improve the oral bioavailability of anti-influenza drugs

DESCRIPTION (provided by applicant): With the concern for an avian influenza pandemic increasing, there is a need to develop antiviral therapies with improved bioavailability. We are developing an enhanced oral delivery platform for anionic small molecule antiviral drugs using zanamivir as our investigational drug. While zanamivir has proven to be a potent and effective inhibitor of influenza neuraminidase and inhibitor of influenza virus replication in vitro and in vivo, it has been difficult to translate into a successful clinical treatment for influenza, due primarily to the poor oral bioavailability of zanamivir. Zanamivir, therefore, is currently administered by inhalation. But even this route of administration is not acceptable to many. This combination of factors has resulted in the limited commercial success of zanamivir (Relenza(r)). The long-term objective of the project is to increase the oral bioavailability for zanamivir and other anionic drugs with poor intestinal absorption. Many drugs and drug candidates exhibit poor oral bioavailability limiting their dosing to injection, infusion or inhalation. At TSRL, we have created carrier molecules that non-covalently bind a drug molecule, and the carrier/drug complex demonstrates better intestinal absorption. Our technology has the potential to convert a wide range of active compounds from parenteral to oral administration, thereby increasing the accessibility and improving the safety profile of the drug product. This is especially important in the treatment of highly contagious respiratory viruses, such as the influenza virus.