ABC transporters
ATP-binding cassette transporters are a family of transmembrane proteins that function in the transort of a wide variety of substrates across extra- and intracellular membranes, including metabolic products, lipids and sterols, and drugs. ABC transporters are involved in tumor resistance, cystic fibrosis, bacterial multidrug resistance and a range of other inherited human diseases.
ADME
ADME is a common acronym for absorption, distribution, metabolism and excretion. ADME studies are among a series of non-clinical safety studies conducted prior to human clinical trials. These studies are part of the evaluation to characterize a drug candidate under the conditions of the supported clinical trial.
AhR
Aryl hydrocarbon receptor. AhRs mediate the induction of CYP1A enzymes by agents such as
b-naphthoflavone, 3-methylcholanthrene, Aroclor 1254 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
aliquot
A portion obtained by dividing the whole into several parts, especially one of two or more samples of a substance that have the same volume or weight.
allelozyme
An allelic (genetic) variant of an enzyme. The term was first used to describe variants of alcohol dehydrogenase, but may be applied to other enzymes.
antibody
A protein produced by B lymphocytes in response to, and interacting specifically with, an antigen. This antigen-antibody reaction forms the basis of immunity, and is exploited in various immunoassays. (Also see
IgG.)
antigen
A substance, usually a protein, that is recognized by the immune system as foreign and that can elicit an immune response, resulting in production of an antibody.
assay
The analysis of a substance or mixture to determine its constituents and the relative proportions of each. This term is synonymous with “test”.
The process by which xenobiotics are chemically modified and converted to water-soluble metabolites that can be readily excreted. Biotransformation is often called metabolism, although the latter term has a broader definition (see
metabolism). The process of biotransformation is divided into two phases called Phase I (oxidation and hydrolysis) and Phase II (conjugation).
blood brain barrier
The blood brain barrier (BBB) is the specialized system of capillary endothelial cells that protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. Unlike peripheral capillaries that allow relatively free exchange of substances across or between cells, the BBB strictly limits transport into the brain through both physical (tight junctions) and metabolic (enzymes) barriers. Thus the BBB is often the rate-limiting factor in determining permeation of therapeutic drugs into the brain. Additionally, BBB breakdown is theorized to be a key component in central nervous system associated pathologies. BBB investigation is an ever-growing and dynamic field studied by pharmacologists, neuroscientists, pathologists, physiologists, and clinical practitioners
CAR
Constitutive androstane receptor. CARs mediate the induction of CYP2B enzymes by agents such as phenobarbital, antihistamines and Aroclor 1254.
clearance
The volume of blood or plasma that is cleared of a substance per time unit through elimination processes.
CMV
Cytomegalovirus
coenzyme
A substance needed by certain enzymes to catalyze reactions. Most vitamins are considered coenzymes.
cofactor
A substance that functions as a co-substrate in an enzyme-catalyzed reaction. For example, NADPH is a cofactor for cytochrome P450-catalyzed reactions.
CYP
Cytochrome P450
Cytochrome P450
Cytochrome P450 (CYP) is a family of membrane-bound hemeproteins that play a key role in the oxidative biotransformation of drugs and a variety of other xenobiotics and endobiotics.
Cytomegalovirus
Cytomegalovirus (CMV) is a herpesvirus that infects directly through mucous membrane contact or via tissue transplant or blood transfusion. Approximately half the adult population in developed countries, and three-quarters of HIV risk groups have been infected with CMV.
cytosol
A subcellular fraction that represents the soluble portion of liver homogenate, and contains numerous drug-metabolizing enzymes, especially those involved in Phase II biotransformation, such as sulfotransferases and glutathione
S-transferases.
DMEM
Dulbecco’s Modified Eagle Medium. DMEM is cell culture medium designed for supporting the growth of a broad spectrum of cell lines.