The understanding that drug metabolites often play a critical role in the efficacy and safety profile of drugs has propelled drug metabolism research to become an integral part of pharmaceutical research and development. Drug metabolism (also known as biotransformation) is a biochemical process in which drugs are converted to more hydrophilic species to facilitate their elimination from the body . Most chemicals, including drugs, are transformed in the human body to a wide variety of products by a host of enzymes present mostly intracellularly, though bacteria in the gastrointestinal tract can metabolize some structures. The reactions catalyzed by drug metabolizing enzymes can be categorized into two groups: phase I functionalization and phase II conjugation . Phase I reactions often involve oxidation, reduction, dealkylation, deamination, and hydrolysis, with less frequent reactions including chiral inversion, rearrangement, and dehydration. Many introduce or unmask a functional group (e.g., –OH, –COOH, –NH2, or –SH) within the molecule. Phase II reactions impart the drug or 368its metabolites with an endogenous molecule such as glucuronic acid, sulfate, amino acids, or glutathione (GSH), which leads in many cases (i.e., methylation and acetylation leads to higher lipophilicity) to an increase in hydrophilicity and a concomitant decrease in the volume of distribution (Vss), resulting in decreased tissue partitioning of the drug. While many of these metabolites are physiologically inactive, some are active either therapeutically or toxicologically. Other undesirable consequences resulting from biotransformation reactions include rapid drug clearance  and drug-drug interactions (DDIs) .