The oral route remains the most common, convenient, economical, and generally safest means for drug administration. Metabolism represents the major means by which the body eliminates drugs. Enzymatic modification of the drug generally produces inactive metabolites with increased polarity and water-solubility to enhance excretion. The gastrointestinal (GI) tract is the first in the sequence of organs that drugs encounter when taken orally. The potential impact of intestinal first-pass metabolism on oral drug disposition has become increasingly recognized. Most drugs are administered as solid dosage forms. Many commonly prescribed drugs undergo extensive first-pass metabolism upon oral administration. CYP4F enzymes catalyze the biotransformation of several endogenous compounds, including arachidonic acid and its leukotriene, prostaglandin, lipoxin, and hydroxyeicosatetraenoic acid derivatives. CYP2J2 is a relatively identified human cytochrome P450 that is expressed predominately in extrahepatic tissues. The Uridine diphosphate-Glucuronosyltransferases are ubiquitous in a number of extrahepatic tissues, including the GI tract.