Altered Drug Metabolism and Transport in Pathophysiological Conditions

Drug metabolism can either lead to detoxification, bio-inactivation and/or elimination of the drug from the body. Metabolism can be broadly categorized into phases I and II. Phase I drug metabolizing enzymes (DMEs) primarily comprise of the Cytochrome (CYP) 450 family of enzymes. CYP3A4 is the most common isoform expressed in human liver and intestine accounting for ~30-60% of CYPs (Nebert & Russell, 2002) More than 50% of the currently marketed drugs are metabolized by CYP3A4 in humans (Guengerich, 1999). Phase II metabolism consists of conjugation reactions forming polar metabolites leading to enhanced excretion. Phase II reactions include glucuronidation (Uridine 5'-diphosphoglucuronosyltransferase, UGT) sulfation (Sulfotransferase, SULT), methylation (Methyltransferase), glutathione conjugation (Glutathione S-transferase, GST), etc. (Jancova et al., 2010; Meyer, 1996).