G. Sowjanya*, S. Ganapaty, Rupakshi Sharma
Department of Pharmaceutical Analysis, Institute of Pharmacy, GITAM Deemed to be University, Rushikonda, Visakhapatnam, Andhra Pradesh, India
*Address for Corresponding Author
Dr. G. Sowjanya,
Department of Pharmaceutical Analysis
Institute of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam – 530045, Andhra Pradesh, India
Metabolite identification and profiling are relevant in several stages of drug discovery & development. Studies modelling both the human and experimental animal metabolism of a drug are useful in the design of toxicological studies. An imperative issue in toxicology is the suitability of the information obtained with experimental animals for human risk assessment. However, the data obtained in animal studies can be better extrapolated to the patient by utilizing bridging studies with invitro models of human drug metabolism. There are two basic categories of in vitro methods for the examination of human liver drug metabolism. The first group of invitro methods consists of the cellular models, which include primary hepatocytes, liver slices, and cell lines. The second group is the utilization of preparations of the drug metabolizing enzymes such as supersomes, cytochrome P450, cytosolic fraction, S9 fraction, human liver microsomes and rat liver microsomes. Invitro studies can identify the species specific metabolic routes, and the experimental animal models that best reflects the potential human exposure to the drug and its metabolites. In this review, detailed procedures, advantages, disadvantages and applications of various invitro metabolite identification methods have been discussed.
Keywords: Metabolite identification, drug discovery & development, toxicology, cellular models, metabolizing enzymes