ADME Glossary
ABC = ATP-binding cassette, a superfamily of membrane transporter proteins that pump various compounds across extra- and intra-cellular membranes. The most known functions of ABC transporters involve pumping of xenobiotic compounds, including drugs, out of the cell cytoplasm.
AOX = Aldehyde oxidase enzyme
ALDH = Aldehyde dehydrogenase enzyme
APCI = Atmospheric pressure chemical ionisation (in mass spectrometry)
Apical membrane = Cell membrane of polarised cells, separated from basolateral membrane by tight junctions, generally facing ‘outwards from the body’.
ATPase = Enzyme catalysing a process involving the hydrolysis of ATP. Various proteins, such as ABC transporters, have ATPase activity.
AUC = Area under the curve. Area under the concentration vs time curve is used as the measure of exposure, e.g., in in vivo pharmacokinetic studies.
Basolateral membrane = Cell membrane on surface of polarised cells adjacent to the basal lamina
BCS = Biopharmaceutical classification system. A system to classify compounds to four categories based on their solubility in gastrointestinal fluids and intestinal wall permeability.
I, high permeability, high solubility; II, high permeability, low solubility; III, low permeability, high solubility; IV, low permeability, low solubility.
Bioavailability (F) = Fraction of administrated drug that reaches the systemic circulation
Blood-brain barrier = A selective permeability barrier that regulates the chemical environment of the central nervous system and protects it from xenobiotics.
Caco-2 = Human colon carcinoma derived cell line used for cell monolayer permeation experiments
Cell suspension = a liquid cell culture medium containing unattached cells
CES = Carboxylesterase enzyme; involved in ester hydrolysis reaction
Clearance = Elimination of a drug from the body, defined as the volume of fluid cleared of drug in a time unit
CLH = The total hepatic clearance [l/min], taking account the liver blood flow
CLint = Intrinsic clearance [l/min], the intrinsic capacity of a system (e.g., the liver) to eliminate the compound. Hepatic CLint can be calculated from total hepatic clearance in vivo by accounting for the liver blood flow or extrapolated from substrate depletion in microsomal or hepatocyte incubations, after taking account the in vitro-in vivo extrapolation scaling factors (MPPGL or hepatocellularity).
CLint, inc = In vitro clearance [µl/min/mg protein or µl/min/million cells], calculated from substrate depletion in microsomal or hepatocyte incubations
Cmax = Maximum concentration
CYP = Cytochrome P450 enzyme, family of membrane bound enzymes active in drug metabolism processes of drugs
DMPK = Drug metabolism and pharmacokinetics
Efflux pump = Cell membrane proteins transporting molecules out from the cell (ABC transporters)
EMA = European Medicines Agency (formerly known as EMEA)
Endogenous = Material (compounds) produced by a cell or an organism
Epithelial cells = Cells on the inner and outer surface of the body
ESI = Electrospray ionisation (in mass spectrometry)
Expression (of a protein) = a process where a protein is produced from a gene (including transcription, translation, and post-translational modifications
Fa = Fraction of dose absorbed
FaSSIF = Fasted state simulated intestinal fluid, an artificial biorelevant media for drug solubility and dissolution experiments
FeSSIF = Fed state simulated intestinal fluid, an artificial biorelevant media for drug solubility and dissolution experiments
FDA = U.S. Food and Drug Administration
FMO = Flavin containing mono-oxygenase, involved in N-oxidation reactions; uses bound flavin as a cofactor
Fg = Fraction of absorbed dose escaping the gut wall first pass metabolism
Fh = Fraction of amount of compound escaping the elimination during a single pass through the liver
Fu = Unbound fraction (in plasma or in incubation)
GSH = Glutathione
GST = Glutathione-S-transferase enzyme; involved in glutathione conjugation reaction
Hepatocellularity = Estimated concentration of liver cells in vivo, equals
Hepatocyte = a major component of the liver
HPLC = High performance liquid chromatography
HTS = High throughput screening
IC50 = Half maximal inhibitory concentration; indicates how much of a particular inhibitor is needed to inhibit a given biological process by half
ICH = International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
In vitro = a process occurring in a test-vial or in a other non-living organism
In vivo = a process occurring in a living organism
IV = Intravenous. Drug administration as injection or infusion to a vein.
Km = Michaelis constant, the substrate concentration that gives half maximal reaction velocity
Ki = The inhibitor constant, the concentration required to produce half maximum inhibition, related to IC50 (depending on the inhibition mechanism; in competitive IC50=Ki[1+([S]/Km)], in non-competitive IC50=Ki)
Lead = Series of (hit) compounds that have suitable potential to become a drug candidate
Lead optimisation = a process where chemical structure of a hit compound is refined to improve its drug-like characteristics (ADME properties), aiming for a drug candidate for preclinical development
LogD = Logarithm of distribution coefficient D of a compound between octanol and buffer layers. logD = log10 [in octanol]/[in water]. Describes the total partition of both ionised and unionised form at a certain pH.
LogP = Logarithm of partition coefficient P of a compound between octanol and buffer layers. logP = log10 [in octanol]/[in water]. Describes partition of the unionized (neutral) form of the compound.
Mass resolution = Ability to separate ions with closely similar mass-to-charge ratio (by mass spectrometer)
MAO = Monoamine oxidase, involved in oxidative deamination, uses bound flavin adenine dinucleotide (FAD) as a cofactor
MDCK = Cell line derived from Madin-Darby canine kidney epithelial cells used for permeation experiments
MDR1 protein = Multi-drug resistance protein, a synonym for P-glycoprotein (P-gp), a transporter protein encoded by ABCB1 gene that pumps xenobiotic compounds (drugs) out of the cell cytoplasm
MPPGL = a scaling factor for microsomal protein per gram of liver
NADPH = Nicotinamide adenine dinucleotide phosphate-oxidase, acts as a cofactor in CYP-enzyme catalysed reactions
NAT = Arylamine N-acetyltransferase, involved in N-acetylation, uses acetyl CoA as a cofactor
NCE = A new chemical entity, a previously undescribed compound
MS = Mass spectrometry
MT = Methyltransferase enzyme; involved in methylation reaction, uses SAM as a cofactor
PAMPA = Parallel artificial membrane permeation assay; non-cell line based membrane assay to evaluate passive permeation of a substance
Papp = Apparent permeability coeffiecient (cm/s); calculated from results obtained from permeation experiments
PAPS = 3'-Phosphoadenosine-5'-phosphosulfate (acts as a cofactor in sulfontransferase reactions)
Permeability = Ability of a compound to diffuse through biological membranes
PBPK = Physiologically based pharmacokinetic modelling, a technique for simulation of pharmacokinetics with a mathematical model built based on anatomy and physiology, and drug metabolism, transport and physicochemistry
P-gp = P-glycoprotein, a member of ABC family of transporter proteins (ABCB1), that pumps xenobiotic compounds (drugs) out of the cell cytoplasm
Pharmacodynamics (PD) = a term describing what the drug does to the body
Pharmacokinetics (PK) = a term describing what the body does to the drug; meaning the concentration-time-dependency of the drug in blood circulation and various other body tissues after a certain dose
pKa = Dissociation constant, a measure of acid strength of the compound. pKa = - log Ka, and for acids (A) the Ka = [H+][A-]/[HA], while for bases (B) Ka = [H+][B]/[HB+].
PO = Per oral. Drug administration via oral route.
Prodrug = Pharmacologically inactive form of the drug that is transformed to its active form after administration (by metabolism). Used to improve the absorption (bioavailability) of the active form.
QH = Liver blood flow
%Q = Clearance compared to liver total blood flow, %Q = 100 % × (CLH/QH),
Robustness = A measure how the test system can tolerate small changes in test conditions
Substrate = A molecule going through a certain reaction catalyzed by an enzyme, i.e., drug-like compound that is transformed to its metabolite
SAM = S-adenosylmethionine, a cofactor for methyltransferase enzyme in methylation reaction
SGF = Simulated gastric fluid, an artificial biorelevant media for drug solubility and dissolution experiments
SULT = Sulfontransferase enzyme; involved in sulfate conjugation reaction, uses PAPS as a cofactor
TOF-MS = Time-of-flight mass spectrometry
t1/2 = Half-life, time in which the (drug) concentration decreases to one half of its initial value
Tmax = The time after drug administration to reach the maximum concentration (Cmax)
UDPGA = Uridine diphosphate glucuronic acid (acts as a cofactor in UGT reactions)
UGT = Uridine 5'-diphospho-glucuronosyltransferase enzyme; involved in glucuronide conjugation reaction, uses UDPGA as a cofactor
UPLC /UHPLC = Ultra high performance liquid chromatography
Vd = Volume of distribution; the ratio of the total amount of the compound in body and the concentration of compound in plasma. A measure quantifying the distribution of a compound between plasma and the rest of the body.
Vehicle = Matrix in which the active component (drug) is administrated as a pharmacological preparation
Vmax = Reaction maximal velocity in incubation (amount unit /time unit, e.g., nmol/[mg microsomal protein×min])
Xenobiotic = Substance not produced by the biological system, e.g., drug