Biotransformation Brochure

Knowledge of the biotransformation pathways of a drug candidate is critical to the smooth progression of both lead candidate selection and the development phases of drug research. Charles River offers a variety of in vitro and in vivo studies with analytical chemistry support to provide metabolite information, either as part of an absorption, distribution, metabolism, and excretion (ADME) package or as a stand-alone study.

Biotransformation describes the conversion of a compound to a metabolite through the actions of enzymes. This can occur by means of intestinal organisms or tissue enzymes. Qualitative and quantitative metabolic differences between species are often apparent. As a result, a crucial stage in drug development is the isolation, analysis and identification of metabolites to establish any differences between drug metabolism in the animals used in preclinical safety programs and humans. The discovery of unique and/or major human metabolites late in development can cause delays and have implications for market approval.

Preliminary in vitro studies often generate information on the number and type of drug metabolites likely to be produced in vivo. Cells or cellular fractions, such as hepatocytes, S9 fraction, and human liver or intestinal microsomes, are used as metabolic systems and provide data regarding the enzyme or enzymes involved.