Evaluation of the metabolism of propranolol by linear ion trap technology in mouse, rat, dog, monkey, and human cryopreserved hepatocytes.
Propranolol is a widely used quality control and validation compound for liver microsome and hepatocyte metabolism studies. A multitude of literature reports describing the identification of propranolol metabolites exists today. However, no literature reports currently exist showing hepatocyte metabolism across the five species commonly used during pre-clinical drug discovery, namely mouse, rat, dog, monkey, and human. Herein, we present full metabolic profiles of propranolol in mouse, rat, dog, monkey and human hepatocytes. As expected, extensive phase I and phase II metabolism was observed across all five species and species-specific metabolites were detected in monkey and dog hepatocytes. Of particular interest was the detection of an N-hydroxylamine glucuronide metabolite in monkey and dog hepatocytes.
Baughman
Todd M
TM
Infectious Diseases CEDD DMPK, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. todd.m.baughman@gsk.com
Talarico
Christine L
CL
Soglia
John R
JR
D000818:Animals; D015925:Cryopreservation; D004285:Dogs; D000882:Haplorhini; D022781:Hepatocytes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D013058:Mass Spectrometry / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D011433:Propranolol / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats
D011433:Propranolol