Dear members

I would like to hear your thoughts on what safety margins you believe we need when evaluating results from ex vivo action potential recordings (e.g. GP papillary muscle APD90).

Any references would also be greatly appreciated.

Also, how big an effect do you consider to be relevant?

Best regards, Morten - H. Lundbeck A/S

Does anybody know a method to study the effects of compounds on gap junctions?

How do others handle the issue of loosing a telemetry animal in a 4×4 Latin square design. For example if you loose one animal after two doses and still have two additional dosing periods.

What is the current practice in the industry when this occurs? One suggestion was to substitute in an animal and simply finish out the study in the normal 4 doses. Another was to substitute in an animal and give 4 more doses. Yet another is to continue on with missing cells. What is your opinion or experience?

I would also like to get the perspective on how you feel these options might impact the statistics.

USDA Policy #3 (Nov 7, 2007) requires the use of pharmaceutical compounds in animals, specifically covered species.  Interested in how other pharmaceutical companies and CROs are handling this new guideline with respect to any and all compounds other than NCEs or NBEs that are administered.  Materials used for analgesia, anesthesia, euthanasia and any animal health medications would most certainly be pharmaceutical grade, but what about reference compounds, competitor compounds and various pharmacological tool compounds used in the performance of many assays?

Prior to candidate recommendation from discovery, most groups conduct some sort of “ancillary” cardiovascular study. The question is in what model?

Could folks share the in vivo model or models that are typically used (eg. dog, monkey, rat, conscious/anesthetized, etc) to support the advancement of a compound into the toxicology phase of development.  Also, if any models used are established in the company, or outsourced.