Journal of Drug Metabolism & Toxicology
Open Access

Gaia Scalabrino

Publications

• Research Article
  Bioactive Indanes: Comparative in vitro Metabolism Study of PH46A, a New Potential Anti-inflammatory Agent and Biosynthesis of its Primary Metabolite PH132
  Author(s): Tao Zhang, Gaia Scalabrino, Neil Frankish and Helen SheridanTao Zhang, Gaia Scalabrino, Neil Frankish and Helen Sheridan
  
  PH46A is the lead of a new class of bioactive indanes with potential for the treatment of inflammatory bowel disease. A qualitative in vitro metabolism profile of PH46A was investigated in preclinical studies, and the rate of its metabolism in cryopreserved hepatocytes prepared from male Sprague Dawley rat, Beagle dog, Cynomolgus monkey and pooled mixed gender human was compared by LC-MS. The clearance order of PH46A was determined to be rat>dog>monkey>human. The species tested which exhibited the closest clearance values to the human was monkey. Following incubation of PH46A with cryopreserved hepatocytes, 5 metabolites were identified, including M1 (keto-PH46), M2 (PH46-OH, PH132), M3 (PH46-diOH), M4 (keto-glucuronide-PH46) and M5 (glucuronide conjugate-PH46). It was found that the human metabolites M2 and M5 were also present in rat, dog and monkey, while M1 was present in.. View More»
  DOI: 10.4172/2157-7609.1000239

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