After intravenous (IV) bolus administration, the drug is distributed to all parts of the body including eliminating and noneliminating organs. In noneliminating organs, the drug can distribute back and forth between the blood and the tissues to maintain the distribution equilibrium, while in eliminating organs, in addition to drug distribution, the drugs can be eliminated leading to reduction in the drug amount in the body. The drug elimination process can be dened as the process by which the drug becomes no longer available to exert its effects in the body. This can happen by excretion of the unchanged drug from the body without any modication of the drug molecule. Examples of unchanged drug excretion include the renal drug excretion in urine, excretion of drugs with bile into the gastrointestinal tract (GIT), lung excretion of volatile drugs during expiration, and excretion of drugs with body secretions such as saliva, sweat, or milk. The other major route of drug elimination is drug metabolism, which involves enzymatic modication of the chemical structure of the drug molecule to form a new chemical entity known as the metabolite. Since the metabolites are inactive molecules in most cases, drug metabolism is considered one of the elimination pathways. However, for few drugs, the metabolites possess therapeutic

and/or adverse effects. Drug metabolism usually occurs in organs that contain the metabolizing enzymes such as the liver, small intestine, kidney, and lungs.