Drug Metabolism and Disposition

Drug Metabolism and Disposition

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Cover of the July 2010 issue of Drug Metabolism and Disposition

Drug metabolism and disposition refers to the processes by which the body absorbs, distributes, metabolizes, and excretes drugs. These processes determine the duration and intensity of a drug's pharmacological action. Understanding these processes is crucial for the development of new pharmaceuticals and for optimizing the use of existing drugs.

Absorption

Absorption (pharmacokinetics) is the process by which a drug enters the bloodstream from its site of administration. The rate and extent of absorption depend on factors such as the drug's formulation, the route of administration, and the presence of food or other substances in the gastrointestinal tract.

Distribution

Once absorbed, drugs are distributed throughout the body. Distribution (pharmacokinetics) involves the transport of drugs via the bloodstream to various tissues and organs. Factors influencing distribution include blood flow, tissue permeability, and the binding of drugs to plasma proteins.

Metabolism

Metabolism (pharmacokinetics) is the process by which the body chemically alters drugs. This usually occurs in the liver through enzymatic reactions. Metabolism can convert active drugs into inactive forms or, conversely, convert prodrugs into their active forms. The primary enzymes involved in drug metabolism are the cytochrome P450 family.

Phase I Reactions

Phase I reactions involve the introduction or unmasking of functional groups on the drug molecule, often through oxidation, reduction, or hydrolysis. These reactions are primarily catalyzed by cytochrome P450 enzymes.

Phase II Reactions

Phase II reactions involve conjugation, where the drug or its Phase I metabolite is linked with an endogenous substance, such as glucuronic acid, sulfate, or glycine. This process generally increases the water solubility of the drug, facilitating its excretion.

Excretion

Excretion (pharmacokinetics) is the process by which drugs and their metabolites are eliminated from the body. The primary routes of excretion are renal (via the kidneys) and biliary (via the liver and bile). Other routes include the lungs, sweat, and breast milk.

Factors Affecting Drug Metabolism and Disposition

Several factors can influence drug metabolism and disposition, including age, genetic factors, liver function, and the presence of other drugs. For example, genetic polymorphisms in drug-metabolizing enzymes can lead to variations in drug response among individuals.

Clinical Implications

Understanding drug metabolism and disposition is essential for predicting drug interactions, optimizing dosing regimens, and minimizing adverse effects. It also plays a critical role in the development of new drugs, as it helps determine the appropriate dosage and frequency of administration.

Related Pages

• Pharmacokinetics
• Pharmacodynamics
• Cytochrome P450
• Drug interaction