Introduction

Webster's Dictionary defines the term pharmacology as "the science of drugs including materia medica, toxicology, and therapeutics; the properties and reactions of drugs especially with relation to their therapeutic value.'' Clinical pharmacology specifically focuses on the study of drugs in humans. A researcher working to develop new drugs at a pharmaceutical company may subscribe to a much narrower definition of pharmacology as the way a chemical entity acts on a specific molecular pathway in the body.

Every drug (chemical) has various properties that affect its pharmacological value. The way in which the drug acts

on the body or target tissue is called pharmacodynamics. The way in which the body acts on the drug is called pharmacokinetics. The relationship between a potential drug's pharmacokinetics and pharmacodynamics (often referred to as PK/PD) is the central core of pharmacological research.

The pharmacodynamics phase corresponds to the way in which a drug binds to receptors, transporters, and channels in order to elicit a particular action from a cell (this is called signal transduction). This is referred to as the "mechanism of action.'' While researchers attempt to determine the mechanism of action of promising compounds in order to better predict therapeutic outcomes and unexpected effects, often times the exact mechanism remains unknown, even after the drug has been approved for use.

The specificity of the drug's interaction with receptors is key. A therapeutic agent needs to be able to interact with the designated target without interfering in other processes and causing severe side effects. Drugs can be broadly categorized as either "agonists" or "antagonists" depending on how they react with receptors. Agonists act directly on the receptors themselves, either reducing the number of active receptors (turning them off) or increasing the number of active receptors (turning them on). Antagonists act indirectly on receptors by reducing the actions of other substances, which act on the receptor sites.

Dose-response is another key aspect of the pharmacodynamic action of a drug. Simply put, this is the relationship between the quantity of the drug and the magnitude of the body's response. The data is typically presented in graphical format and may be referred to in the literature as the "dose-response curve.'' The slope of the curve is generally an indication of the change in response per unit dose of the drug. This is one way in which researchers can determine the appropriate dosage needed in order to obtain the desired therapeutic effect.

Dose-response is dependent upon the actual amount of the compound that reaches the intended target site after administration. The term pharmacokinetics refers to the factors that influence this amount. There are four basic pharmacokinetic measures: absorption, distribution, metabolism, and elimination. These parameters are often referred to as ADME. Each parameter can be calculated using a variety of formulas. Absorption refers to the way in which the compound moves from the site of administration into systemic circulation. This can vary depending on the drug's formulation, route of administration, and other physiochemical properties of the drug. After a drug enters systemic circulation, it is then distributed by the bloodstream to the body's tissues. Metabolism occurs in the liver, where enzymes break the compound down into its various components, or metabolites. Some of these metabolites may be pharmacologically active. This is the basis of compounds called pro-drugs, where it is only the metabolite, and not the drug itself, that has therapeutic properties. Elimination is generally carried out by the kidneys (renal excretion), although some drugs may be excreted in bile (biliary excretion).

Most of the major biomedical literature databases utilize specific indexing terms to reference pharmacokinetic and pharmacodynamic information. MEDLINE® introduced the term pharmacokinetics in 1988 as both a medical subject heading and subheading. Pharmacokinetics and pharmacody-namics are both EMTREE vocabulary terms and are used as subheadings in BIOSIS®.

Drug monographs are also an important source of clinical pharmacology data. Publications such as The Physicians' Desk Reference, Martindale Complete Drug Reference, and Drug Facts and Comparisons generally provide pharmacoki-netic information for each referenced product. New Drug Applications and package labels also contain complete clinical pharmacology data.

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