Drug Metabolism
Drug Metabolism Studies
Defining Metabolic Clearance Pathways Through In Vitro Models
As part of our comprehensive portfolio of ADME-Tox research services we provide the following drug metabolism studies.
Metabolite Identification (Met ID)
In vitro Met ID studies determine and characterize metabolites and biotransformation routes of test articles.
Metabolic Stability
In vitro metabolic stability studies determine the metabolic clearance of a compound over time.
CYP Reaction Phenotyping
In vitro CYP reaction phenotyping studies identify the CYP enzymes involved in drug metabolism.
UGT Reaction Phenotyping
In vitro UGT reaction phenotyping studies identify the UGT enzymes involved in drug metabolism.
The Basics of Drug Metabolism
The liver and intestine are the major contributors to drug metabolism and disposition. Following gut absorption and metabolism the portal vein carries blood and parent compounds from the gastrointestinal tract to the liver. Compounds are taken up into the hepatocytes through passive diffusion and/or active uptake by drug transporters present on the basolateral membrane of the hepatocytes.
Once inside the hepatocyte, compounds may undergo metabolism, and the parent and/or generated metabolites may be excreted across the canalicular membrane into the bile or across the basolateral membrane into systemic circulation. Our drug metabolism studies help you identify metabolic pathways, understand the hepatobiliary disposition, and predict pharmacological and toxicological properties of drugs and their metabolites.
Our Approach to Evaluating Drug Metabolism
As an initial step in in vitro drug metabolism programs we identify the enzymes that significantly contribute to the metabolism of drug candidates. We implement metabolic stability studies to measure intrinsic clearance and determine the extent to which a drug will be metabolized. And we conduct metabolite identification studies to determine the number, putative structure, and proposed biotransformation pathways of metabolites produced as a result of interaction with drug-metabolizing enzymes.
The results of metabolic stability studies and metabolite identification studies frequently inform other studies that are part of comprehensive ADME-Tox programs, such as reaction phenotyping studies to identify enzymes involved in biotransformation of a drug, which are essential to understanding drug-drug interaction liability potential.
Species Comparison
As part of metabolism programs, we also design and implement species comparison studies to help select a preclinical model that most closely resembles human in its metabolic profile. Additionally, comparing different species to human data helps identify any human-specific metabolites.