Seite - (000095) - in Biomedical Chemistry: Current Trends and Developments

Predict drug-drug interaction potential. Microsomes They are the most widely used subcellular fractions for drug metabolism studies, with the advantages of being inexpensive and easy to handle while containing the major drug metabolism enzymes, e.g., CYPs and UGTs. It is necessary to supplement the subcellular fractions with enzymes cofactors to initiate the various enzymatic reactions. By including or excluding certain co-factors, one can pinpoint the involvement of certain metabolic pathways for a given drug candidate. Compounds are quantified after predefined times of incubation by HPLC. Both reversible inhibition and time-dependent inhibition studies provide information on the possibility of the drug candidate being a perpetrator of drug-drug interaction for a co-administered drug. Determine intrinsic clearance, a useful parameter for facilitating the screening process for stable compounds and for establishing an in vitro correlation between animals and humans. Identification of the main metabolites. Assess extra-hepatic metabolism and further strengthen the in vitro prediction of total body clearance by using microsomes from various tissues. Microsomal assays are the default assays for metabolism and DDI studies at the drug discovery stage. Cell culture and cell lines Primary cultures of hepatocytes: They carry enzymes and co-factors at physiological concentrations and provide a drug metabolism environment that closely mimics the in vivo conditions; however they have a limited life span and differentiation ability. Immortalized human hepatic tumor cell lines (HepG2 or HepaRG) They present lower cost and higher ease of storage than Identification of the metabolites generated. Predict drug clearance; Predict DDI potential of drug candidates. ‘Gold standard’ for conducting CYP induction studies before (non)-clinical investigations.