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Thursday, May 25, 2017

A case in point

XBL Metabolism Studies Clear Way For Drug Approval

A sponsor's drug product was in advanced clinical testing while long term toxicology studies were underway in multiple species. When one long term toxicology study in dogs produced unexpected gastro-intestinal irritation, including severe bowel problems, the clinical studies were placed on hold.

The challenge

Could XBL assist with understanding the problem at hand, and assist the Sponsor in determining whether or not this adverse reaction in dogs was relevant to human exposure?

The methods

XBL's scientific staff reviewed the metabolite profiles from multiple species and multiple matrices both in vitro and in vivo, with particular attention to fecal metabolites. Metabolite radioprofile as well as LC/MC/MS identity data were evaluated for all toxicology species and compared to the human metabolite profiles using XBL's state-of-the-art instrumentation.

The result

As part of the intensive search and comparison of metabolites, a unique canine metabolite in feces was identified that had not been previously identified. This unique fecal metabolite was not seen in any other species, and other species did not demonstrate the gastro-intestinal symptoms observed. The metabolite in question was isolated, identified and found to cause the observed GI symptoms in dogs.

The impact

The clinical hold was removed, clinical studies completed, and the drug product in question was ultimately approved for human use.

XBL. Invested in science. Invested in your success.