Figure 1: Steps involved in drug metabolism and disposition. (1) Uptake transporter mediates drug entry into the cell. (2) Drug activates xeno-sensing NR in the cytoplasm or nucleus. (3) NR binds to XREs in target genes that are involved in drug metabolism and clearance. (4) Coactivator association with the DNA-bound NR and a cascade of activating steps, which culminate in gene transcription for DMEs, transporters. (5) Expression of phase 0-III mediators. (6) Phase I enzyme adds water-soluble functional groups to the drug structure. (7) A phase II conjugative transferase adds hydrophilic groups to drug/drug metabolite. (8) Phase III efflux transporter moves to plasma membrane. (9) Transporter- assisted drug efflux. (10) Drug clearance through biliary and urinary excretion.