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Barbeau Pharma Announces That Its Studies Of The Cardiotoxicity Of Drug Metabolites Are Consistent With Newly Issued FDA Recommendations For Assessing Pharmaceutical Cardiac Risk

Posted on: Tuesday, 22 November 2005, 09:00 CST

Barbeau Pharma, Inc. (BPI), a specialty pharmaceutical company focused on proprietary technologies to transform today's problem drugs into differentiated value-added medicines, announces that its studies of the cardiotoxicity of drug metabolites are consistent with the Food and Drug Administration's (FDA's) newly published guidelines for cardiac risk assessment of human pharmaceuticals.

The Company recently coauthored a presentation at the 5th Annual Meeting of the Safety Pharmacology Society held in Mannheim, Germany that described 1) considerable proarrhythmic activity of hydroxylated (oxidized) imipramine metabolites in contrast to low proarrhythmic activity for imipramine, the parent drug, at clinically relevant plasma concentrations and 2) the major contribution by calcium and sodium cardiac ion channels to cardiac conductance disturbances of hydroxylated imipramine metabolites.

The presentation reported the results of studies involving the Langendorff Isolated Perfused Rabbit Heart model performed by CorDynamics, Inc. of Chicago. Donald L. Barbeau, founder and Chief Scientific Officer of BPI, and Dr. Michael Gralinski, CEO of CorDynamics and cofounder and past President of the Safety Pharmacology Society coauthored the presentation with Elaine J. Tanhehco of CorDynamics and Eric Gricius of BPI.

Mr. Barbeau commented, "The potential role of drug metabolites in causing drug induced cardiotoxicity is not a new concept; however, the industry has been preoccupied with parent drugs as the potential cause of cardiac conduction defects and with the potassium channel as a primary basis for proarrhythmic activity. Also, in-vitro analysis of proarrhythmic potential has produced conflicting data with in-vivo analysis because cardiac cells and tissues have limited capacity for drug metabolism, and in-vitro studies using only the parent substance do not provide information on the effects of metabolites."

While in-vitro testing has focused cardiac risk assessment on parent compounds and potassium channels (hERG), the new industry wide FDA guidelines recommend nonclinical testing of proarrhythmic activity of metabolites as well as parent drugs, and the contribution of sodium cardiac ion channels in addition to the potassium ion channel.

Dr. Gralinski noted, "Given our report that oxidized drug metabolites of imipramine are primarily responsible for cardiac conductance defects and severe arrhythmias through multiple cardiac ion channels (e.g. calcium and sodium), we strongly support and welcome the recently issued FDA guidelines which are consistent with the findings of our studies."

Mr. Barbeau added, "At BPI the Company's proprietary ECLYPS(TM) technology is already being applied to develop prodrugs to address adverse cardiac side effects by masking the production of cardiotoxic drug metabolites."

The Mannheim presentation underscores Barbeau Pharma's progress with BPI-205, the first drug being developed using the Company's ECLYPS(TM) platform. "By applying our ECLYPS(TM) technology to alter the metabolic pathway of imipramine to inhibit the formation of cardiotoxic hydroxylated metabolites, BPI-205 is being developed as monotherapy for the treatment of nocturnal enuresis (bedwetting), a major unmet medical need," said Mr. Barbeau.

Historically, imipramine has been used as an adjunctive therapy in combination with other incontinence drugs to treat nocturnal enuresis in children. However, imipramine is not approved for use alone to treat nocturnal enuresis in either children or adults due to a poor side effect profile, particularly its cardiotoxicity.

About Barbeau Pharma, Inc.

Barbeau Pharma, Inc. is a specialty pharmaceutical company focused on the development of differentiated, value-generating therapeutics for market segments of unmet medical need. Led by highly experienced management, the Company's growth strategy centers on its ability to transform in-the-market therapies into new proprietary versions with enhanced medical and market values and representing possible approvals for entirely new indications.

In addition to product specific reformulations, Barbeau's development pipeline is supported by two leading-edge proprietary and patented technology platforms. One is a prodrug platform, designated ECLYPS(TM), with the potential to reduce adverse side effects, particularly cardiotoxicity, of many currently marketed drugs. The second is a Mucosal Adhesive Drug Delivery System, or MADDS(TM), that is designed to allow site-specific delivery of drugs to inflamed tissues in various mucous membranes throughout the body. Barbeau also maintains a tremendous degree of expertise in prodrug design which it plans to utilize in its continued expansion of its research programs.

In almost all instances, the Company intends to pursue regulatory approvals through the submission of 505(b)(2) New Drug Applications (NDA), partly based on data contained in a previously approved NDA or data generated by third parties. In many cases Barbeau plans on augmenting its regulatory filings with its own data from preclinical and, sometimes, clinical studies. Such studies would be confirmatory in nature and, therefore, involve less risk, lower cost, and speeder time to market than is typical of the more traditional drug discovery and development process.

Additional information is available on the internet at www.BarbeauPharma.com/

Source: Business Wire

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