Page - (000092) - in Biomedical Chemistry: Current Trends and Developments

porous filters in 6-, 12-, 24- or 96-well plates; Papp is determined from apical to basolateral sides and vice- versa. Compound quantification by HPLC. permeability; Understand mechanisms underlying intestinal absorption; Identification of NCEs that are substrates or inhibitors of the intestinal efflux transporter, P-glycoprotein. Identify efflux transporters involved in compounds intestinal absorption. Toxicity studies. Ussing chamber Uses intestinal membrane from mice or rats; Segments of small Intestine are mounted in the chamber with oxygenated buffer surrounding it for approximately 3 h. Papp is determined from apical to basolateral sides and vice- versa. Compound quantification by HPLC with simple sample preparation for bioanalysis. Screen NCEs in accordance to their permeability through animal intestinal membrane; Evaluation of absorption and understand the mechanisms underlying intestinal absorption Identify efflux transporters involved in compounds intestinal absorption. Evaluation of specific transport mechanisms, enhancing strategies on a mechanistic basis; Evaluation of toxicity of compounds. Transporter in vitro models Caco-2 Caco-2 cells undergo enterocytic differentiation and become polarized in culture (usually for 21 days), resembling human intestinal epithelium in transporter expression and tight junction formation. Bi-directional studies and compound quantification by HPLC with simple sample preparation for bioanalysis. Determination of efflux coefficient. Evaluate the efflux transport via P-glycoprotein and BCRP. Identification of P- glycoprotein substrates and inhibitors in drug discovery. Evaluation of drug-drug interaction potential.