The pharmacology dictionary, in two languages.

The arithmetic difference between the event rate in the control group and the event rate in the treated group, expressing the absolute benefit of a treatment over a defined period.

The process by which a drug enters the bloodstream from the site of administration, such as the gastrointestinal tract, skin, or lungs.

A first-order rate constant (Ka) that describes the rate at which a drug is absorbed from the site of administration into the systemic circulation.

The ratio of drug exposure (concentration or AUC over a dosing interval) at steady state to that after the first dose, describing how much a drug accumulates with repeated dosing.

A highly porous, finely powdered carbon adsorbent given orally or by nasogastric tube that binds many drugs and toxins in the gut lumen, limiting their systemic absorption and, with repeated doses, enhancing the elimination of some.

A product of drug metabolism that has pharmacological activity of its own, which may be similar to, greater than or different from that of the parent drug.

The substance in a medicinal product that is responsible for its pharmacological activity, as distinct from the excipients; in manufacturing terms it is the drug substance produced under GMP.

A numeric value, assigned to each allele and summed across a diplotype, used mainly for CYP2D6 to translate genotype into a predicted metabolizer phenotype.

A combined effect of two drugs acting on the same endpoint that equals the effect predicted from their individual dose–response relationships, as if one drug were partly substituted for the other.

A noxious and unintended response to a medicinal product in which a causal relationship with the drug is at least a reasonable possibility.

Any untoward medical occurrence in a patient or clinical-trial subject given a medicinal product, whether or not it is considered causally related to the treatment.

The strength of binding between a drug and its receptor or target, determined by the rates of association and dissociation and usually expressed as the equilibrium dissociation constant (Kd) or its negative logarithm (pKd).

A drug or endogenous substance that binds to a receptor and activates it, producing a biological response; it possesses both affinity and efficacy (intrinsic activity).

A ligand that binds to a site on a receptor distinct from the orthosteric (endogenous agonist) site and changes the receptor's affinity for, or response to, the orthosteric agonist.

A severe, potentially life-threatening systemic hypersensitivity reaction of rapid onset that causes airway, breathing or circulatory compromise, usually but not always with skin or mucosal changes.

A drug that binds to a receptor or other target without activating it (affinity but no efficacy) and thereby prevents or reduces the response to an agonist.

A clinical syndrome caused by blockade of muscarinic acetylcholine receptors, characterised by delirium, tachycardia, hyperthermia, mydriasis, dry flushed skin, urinary retention and reduced bowel sounds.

A substance that counteracts the effects of a poison or drug overdose by preventing its absorption, binding or inactivating it, antagonising it at its site of action, enhancing its elimination or reversing its toxic effects.

The integral of the plasma drug concentration–time curve, measuring total systemic exposure to a drug over a specified interval or from zero to infinity; expressed in concentration × time units (e.g. mg·h/L).

The WHO system that classifies active substances into five hierarchical levels according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties.

Induction by a drug of the enzymes responsible for its own metabolism, so that its clearance increases and its concentrations fall over time during continued dosing at the same dose.

The fraction of an administered dose that reaches the systemic circulation unchanged, and the rate at which it does so; by definition, bioavailability is 1 (100%) for an intravenous dose.

The absence of a significant difference in the rate and extent of absorption of the active substance when two pharmaceutically equivalent or alternative products are given at the same molar dose under similar conditions.

A scientific framework that classifies drug substances into four classes according to their aqueous solubility and intestinal permeability, the two main determinants of the rate and extent of oral absorption.

A biological medicine highly similar to an already authorized reference biological product, with no clinically meaningful differences in quality, safety or efficacy, as shown by a comprehensive comparability exercise.

A selective barrier formed by brain capillary endothelial cells joined by tight junctions and supported by pericytes and astrocyte end-feet, which restricts the passage of drugs and solutes from blood into the central nervous system.

The calculated external surface area of the body in square metres, estimated from height and weight and used to scale doses of cytotoxic and some other drugs and to index GFR.

A warning displayed in a bordered box at the top of US prescribing information to highlight serious or life-threatening risks, or measures essential to reduce them.

Drug-induced injury to or dysfunction of the heart, including left ventricular dysfunction and heart failure, arrhythmias, myocardial ischemia, myocarditis, and valvular or pericardial disease.

An observational study that starts from people with a given outcome (cases) and comparable people without it (controls) and compares their past exposure to a suspected cause, such as a drug.

The formation of a stable ring-shaped complex between a metal ion and a molecule bearing two or more donor groups; in pharmacology it underlies both metal antidotes and important absorption interactions.

Inactivation of a drug by direct chemical combination with another substance to form an inactive complex, independently of receptors or physiological effects.

A clinical scoring system that grades the severity of chronic liver disease, mainly cirrhosis, from five variables into classes A, B and C.

A clinical syndrome of excess acetylcholine activity at muscarinic and nicotinic receptors, most often from acetylcholinesterase inhibition, producing copious secretions, bronchospasm, bradycardia, miosis, fasciculations and weakness.

The study of how drug effects and pharmacokinetics vary with biological time, particularly circadian rhythms, and of how drugs influence these rhythms.

The rate at which a drug is removed from the body, primarily by the liver and kidneys, representing the volume of plasma cleared of the drug per unit time.

It is the branch of science that comprehensively examines the relationship of drugs that have reached the clinical trial phase on volunteer patients and healthy individuals in all aspects.

An equation that estimates creatinine clearance in adults from age, body weight, sex and serum creatinine, and is widely used to guide renal dose adjustment.

An observational study that follows groups of people defined by their exposure (e.g., to a drug) over time and compares the incidence of outcomes between exposed and unexposed groups.

A mathematical model that represents the body as one or more kinetically homogeneous, interconnected compartments, used to describe and predict drug concentration–time profiles.

Reversible antagonism in which the antagonist binds to the same site as the agonist, so the block can be overcome by raising the agonist concentration; the agonist curve shifts to the right in parallel without a fall in maximal response.

A range of values, calculated from sample data, that is expected to contain the true population value of an estimate with a stated level of confidence, conventionally 95%.

The time required for the plasma (central compartment) concentration of a drug to fall by 50% after stopping a continuous infusion of a given duration, the 'context' being the duration of the infusion.

A condition or circumstance in which a drug should not be used because the risk of harm clearly outweighs the expected benefit; a relative contraindication calls for caution rather than outright avoidance.

A peer-reviewed, evidence-based prescribing recommendation issued by the Clinical Pharmacogenetics Implementation Consortium for a specific gene–drug pair.

The volume of plasma cleared of creatinine per unit time, used as a clinical index of glomerular filtration rate and as the basis of most renal dosing recommendations.

The occurrence of a hypersensitivity reaction to a drug in a patient sensitised to a different drug, because both share a structural determinant or trigger the same reaction pathway.

A cytochrome P450 enzyme that activates the prodrug clopidogrel to its antiplatelet metabolite and also metabolises proton pump inhibitors and several other drugs.

A highly polymorphic cytochrome P450 enzyme that metabolises a large number of drugs, including several opioids and antidepressants, and activates key prodrugs.

The most abundant cytochrome P450 isoform in the human liver and small-intestinal epithelium, responsible for the oxidative metabolism of a large proportion of clinically used drugs.

A superfamily of heme-containing monooxygenase enzymes, located mainly in the endoplasmic reticulum of hepatocytes and enterocytes, that catalyze most phase I oxidative drug metabolism.

A parenteral preparation, usually given intramuscularly or subcutaneously, that forms a reservoir at the injection site from which the drug is released slowly over weeks to months.

The planned and supervised process of reducing the dose of, or stopping, medicines that may be causing harm or are no longer providing sufficient benefit.

The equilibrium constant for dissociation of a drug–receptor complex, equal to the free drug concentration at which half of the receptors are occupied at equilibrium; a lower Kd means higher affinity.

The process by which a solid drug passes into solution in a solvent such as gastrointestinal fluid; for solid oral dosage forms it is a prerequisite for absorption and often its rate-limiting step.

The reversible transfer of a drug from the bloodstream into the interstitial and intracellular fluids and tissues of the body after it has reached the systemic circulation.

The physical form in which a drug is manufactured and administered, combining the active substance with excipients, for example a tablet, capsule, solution, suspension, injection, cream, transdermal patch or inhalation powder.

A graph relating the dose or concentration of a drug to the magnitude of its effect (graded curve) or to the proportion of a population showing a specified all-or-none response (quantal curve).

The stepwise adjustment of a drug's dose, usually upwards, according to therapeutic response and tolerability until the target effect or target dose is reached.

The time between successive doses in a multiple-dose regimen, denoted τ (tau); together with the dose, it defines the dosing rate.

A study design in which neither the participants nor the investigators treating or assessing them know which treatment each participant receives, to minimize performance and assessment bias.

The gene encoding dihydropyrimidine dehydrogenase, the rate-limiting enzyme for inactivating fluoropyrimidine chemotherapy drugs, whose deficiency risks severe toxicity.

A severe, delayed, T-cell-mediated drug hypersensitivity syndrome with fever, extensive rash, lymphadenopathy, haematological abnormalities such as eosinophilia, and internal organ involvement.

A substance or product used, or intended for use, to modify or explore physiological systems or pathological states for the benefit of the recipient, that is, to prevent, diagnose, treat or relieve disease.

The early research process of identifying a disease-relevant biological target and finding and optimizing a molecule that modulates it, to yield a candidate suitable for development.

A situation in which a drug worsens a coexisting disease or condition, or in which a disease alters a drug's pharmacokinetics or pharmacodynamics so that it becomes less effective or more toxic.

A change in the magnitude or duration of a drug's effect, or in its concentrations, caused by the concurrent or prior administration of another drug.

An alteration of a drug's absorption, disposition or effect by food, specific food constituents or beverages, or an alteration of nutritional status by a drug.

An adverse drug reaction that clinically resembles allergy; when a specific immunological mechanism (IgE or T cells) is demonstrated it is termed drug allergy, otherwise non-allergic hypersensitivity.

The enzymatic biotransformation of drugs and other xenobiotics into metabolites that are usually more polar and more readily excreted, occurring mainly in the liver.

A membrane protein that moves drugs across cell membranes, either into cells (uptake) or out of them (efflux), and thereby influences absorption, distribution and elimination.

The capacity of a drug to produce a response once bound to its receptor; in clinical terms, the maximal effect (Emax) a drug can produce, however much the dose is increased.

The irreversible removal of a drug from the body, comprising its metabolism (biotransformation) to other chemical species and the excretion of unchanged drug or its metabolites.

The time required for the plasma concentration of a drug to decrease by 50% during the elimination phase, reflecting how long the drug remains active in the body.

A first-order rate constant (Ke or Kel) that quantifies the fraction of drug eliminated from the body per unit time, used to calculate half-life.

Measures that increase the removal of an already absorbed drug or toxin from the body beyond its intrinsic clearance, used in selected poisonings to shorten exposure and reduce toxicity.

A polymer coating on tablets, capsules or pellets that resists dissolution in acidic gastric fluid and dissolves at the higher pH of the small intestine, delaying drug release until the dosage form has left the stomach.

The cycle in which a drug or its conjugated metabolite is excreted in bile into the intestine, reabsorbed (after deconjugation, if conjugated) and returned to the liver via the portal circulation.

An increase in the amount and activity of a drug-metabolizing enzyme or transporter, usually through enhanced gene transcription, caused by repeated exposure to a drug or other xenobiotic.

A reduction in the activity of a drug-metabolizing enzyme by a co-administered drug or other substance, which lowers the clearance of drugs dependent on that enzyme and raises their concentrations.

An estimate of glomerular filtration rate calculated from serum creatinine and/or cystatin C together with age and sex, conventionally expressed per 1.73 m² of body surface area.

Describes experiments on living cells, tissues or fluids removed from an organism and studied outside it under conditions that preserve their function, often after the organism has received a drug (Latin, 'out of the living').

Any constituent of a medicinal product other than the active substance, added to enable manufacture, maintain stability, control release, improve acceptability or aid administration.

The removal of unchanged drug or its metabolites from the body, principally in urine and in bile (faeces), and to a lesser extent in exhaled air, sweat, saliva and breast milk.

A pharmacokinetic process where the rate of drug elimination (or absorption) is proportional to the drug's concentration, leading to exponential decline over time.

The metabolism of a drug in the liver (or gut wall) before it reaches systemic circulation, often reducing the bioavailability of orally administered drugs.

A situation in which the absorption rate constant is smaller than the elimination rate constant (ka < ke), so that the terminal slope of the plasma concentration–time curve reflects absorption rather than elimination.

A member of the largest family of cell-surface receptors, a single polypeptide with seven transmembrane α-helices that transduces ligand binding into intracellular signals by activating heterotrimeric G proteins.

An X-linked inherited deficiency of glucose-6-phosphate dehydrogenase that leaves red blood cells vulnerable to oxidative stress, risking acute haemolysis with certain drugs.

A medicinal product with the same qualitative and quantitative composition in active substance(s) and the same pharmaceutical form as a reference product, whose bioequivalence with that product has been demonstrated.

A DNA sequence variation, such as a single-nucleotide change or a copy-number variant, present in more than about 1% of a population.

The property of a chemical or physical agent to damage genetic material, causing gene mutations, structural chromosome aberrations or changes in chromosome number that may lead to cancer or heritable defects.

A phase II conjugation reaction in which UDP-glucuronosyltransferases (UGTs) transfer glucuronic acid from UDP-glucuronic acid to a hydroxyl, carboxyl, amine or thiol group on a drug or metabolite.

An international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials, ensuring that participants' rights, safety and well-being are protected and that trial data are credible.

The part of pharmaceutical quality assurance that ensures medicines are consistently manufactured and controlled to the quality standards appropriate to their intended use and required by the marketing authorization.

An interaction in which furanocoumarins in grapefruit juice irreversibly inhibit intestinal CYP3A4, increasing the oral bioavailability of drugs that undergo extensive first-pass metabolism by this enzyme.

The concentration of a drug that produces 50% of its own maximal effect (Emax); the standard measure of agonist potency in concentration–response studies.

The concentration of an inhibitor that reduces a specified biological or biochemical activity (e.g. enzyme activity, ligand binding or cell growth) by 50% under the given assay conditions.

The ratio of the hazard (instantaneous event rate) in one group to that in another, usually estimated from time-to-event data with a Cox proportional hazards model.

An equation relating the pH of a solution and the pKa of a weak acid or base to the ratio of its ionised and un-ionised forms, used to predict drug ionisation, absorption and distribution.

The component of total clearance due to hepatic metabolism and biliary excretion; the volume of blood cleared of drug by the liver per unit time.

The fraction of drug entering the liver in the blood that is irreversibly removed during a single pass through the organ, ranging from 0 (no extraction) to 1 (complete extraction).

Liver injury caused by a drug, herbal or dietary supplement or other chemical, ranging from asymptomatic aminotransferase elevation to cholestasis, hepatitis and acute liver failure.

An interaction between a herbal medicine or botanical supplement and a conventional drug that alters the drug's pharmacokinetics or pharmacodynamics.

A human leukocyte antigen allele strongly associated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis, most prevalent in Southeast and South Asian ancestry.

A human leukocyte antigen allele strongly associated with a severe, immune-mediated hypersensitivity reaction to the antiretroviral drug abacavir.

A height- and sex-based estimate of body weight associated with normal body composition, used as a dosing weight for some drugs, particularly in obesity, and to set ventilator tidal volumes.

An uncommon, qualitatively abnormal response to a drug that is not explained by its known pharmacology, occurs in only a small proportion of exposed patients and is not clearly dose-related.

A dosage form designed to release the active substance promptly after administration, without deliberate modification of the release rate, so that absorption is governed mainly by dissolution and gastrointestinal physiology.

Experiments or studies performed using computer simulations, modeling, or computational methods to predict biological processes without physical testing.

Experiments or studies performed outside a living organism, typically in a controlled laboratory environment such as a test tube or petri dish using cells, tissues, or biological molecules.

Experiments or studies conducted within a living organism, such as in animals or humans, to observe effects in a complete biological system.

A disease, condition or clinical situation in which the use of a drug is appropriate; approved indications are those accepted by the regulator and stated in the product's authorised information.

A person's voluntary agreement to take part in research or to undergo treatment, given after receiving and understanding adequate information about its purpose, procedures, risks, benefits and alternatives.

The equilibrium dissociation constant of an inhibitor from its enzyme, receptor or transporter; an assay-independent measure of inhibitor affinity, with lower Ki values indicating more potent inhibition.

An analysis strategy in which all randomized participants are analyzed in the groups to which they were originally assigned, regardless of the treatment actually received, adherence or withdrawal.

A CPIC phenotype describing a person with reduced drug-metabolising enzyme activity, typically from one non-functional or decreased-function allele plus one normal-function allele.

A unique, globally recognized generic name assigned by the World Health Organization to a pharmaceutical substance, which is public property and cannot be registered as a trademark.

The ability of a drug, once bound, to activate its receptor and produce a response, expressed relative to a full agonist on a scale from 0 (antagonist) to 1 (full agonist); inverse agonists have negative values.

A ligand that binds to a receptor with constitutive (ligand-independent) activity and reduces that basal activity, producing an effect opposite in direction to that of an agonist.

The accumulation of a weak acid or weak base on the side of a membrane where it is more ionised, because only the un-ionised form diffuses freely across lipid membranes.

The delay between drug administration and the first appearance of measurable drug in the systemic circulation, before absorption begins.

A molecule with confirmed, reproducible activity at a chosen target and acceptable drug-like properties that serves as the chemical starting point for optimization into a drug candidate.

Any molecule, such as a drug, hormone or neurotransmitter, that binds to a specific site on a receptor or other macromolecule; binding alone does not imply activation or blockade.

A transmembrane ion channel that opens (or, less often, closes) directly when a specific ligand, usually a neurotransmitter, binds to it, producing rapid changes in membrane potential within milliseconds.

Pharmacokinetic behaviour in which parameters such as clearance, volume of distribution and half-life do not change with dose or time, so that plasma concentrations and AUC increase in direct proportion to dose.

A spherical vesicle of one or more phospholipid bilayers enclosing an aqueous core, used as a drug carrier that holds hydrophilic drugs in the core and lipophilic drugs within the bilayer.

An initial dose, or series of doses, larger than the maintenance dose, given to reach the target plasma concentration rapidly instead of waiting 4–5 half-lives for accumulation.

The dose given at regular intervals, or the rate of a continuous infusion, that replaces the amount of drug eliminated and keeps the concentration at the desired steady-state level.

The license granted by a competent regulatory authority that allows a medicinal product to be placed on the market, based on assessment of its quality, safety and efficacy for defined indications and conditions of use.

The highest (peak) drug concentration observed in plasma after administration of a dose, read directly from the measured concentration–time profile.

Irreversible or quasi-irreversible enzyme inactivation in which the enzyme converts the inhibitor into a reactive intermediate that binds covalently or tightly to it, so activity returns only as new enzyme is synthesized.

The specific biochemical interaction through which a drug produces its pharmacological effect, usually binding to a defined molecular target such as a receptor, enzyme, ion channel or transporter.

The dose of a drug that produces a specified effect in 50% of a population (quantal definition) or, in graded dose–response studies, the dose producing 50% of the maximal effect.

The dose of a substance expected to cause death in 50% of a test animal population under defined conditions of species, route and observation period; a statistical measure of acute toxicity.

The extent to which a patient's medication-taking behaviour corresponds with the recommendations agreed with the prescriber.

Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of a healthcare professional, patient or consumer.

A statistical method that combines the quantitative results of several independent studies addressing the same question to produce a pooled estimate of effect with greater precision.

A condition in which an increased fraction of hemoglobin contains oxidized ferric (Fe³⁺) iron; this methemoglobin cannot carry oxygen and shifts the dissociation curve to the left, impairing tissue oxygen delivery.

A nonlinear pharmacokinetic model describing drug elimination that transitions from first-order at low concentrations to zero-order at high concentrations due to enzyme saturation.

A dosage form in which the rate, timing or site of drug release is deliberately altered from that of a conventional product, as in prolonged-release, delayed-release and pulsatile preparations.

A 10-item questionnaire that estimates the probability that an adverse event was caused by a drug, classifying the relationship as definite, probable, possible or doubtful.

A drug for which small differences in dose or blood concentration may lead to serious therapeutic failure or serious adverse drug reactions.

Drug- or chemical-induced damage to kidney structure or function, presenting as acute kidney injury, tubular dysfunction, electrolyte disturbances or progressive chronic kidney disease.

The highest tested dose or exposure level at which no biologically or statistically significant increase in adverse effects is observed compared with controls in a toxicity study.

The occurrence or worsening of symptoms, including adverse effects, that results from negative expectations about a treatment rather than from its pharmacological action.

Antagonism that cannot be overcome by increasing the agonist concentration, because the antagonist binds irreversibly or acts at a site or step distinct from agonist binding; the maximal agonist response is reduced.

A trial designed to show that a new treatment is not unacceptably worse than an active comparator, i.e., that any loss of efficacy does not exceed a prespecified non-inferiority margin (Δ).

The CPIC phenotype describing a person with two fully functional alleles of a drug-metabolising enzyme gene, giving the expected, population-typical level of enzyme activity.

The average number of patients who need to be treated with an intervention for a specified period for one additional patient to experience a particular harm compared with the control treatment.

The average number of patients who need to be treated with an intervention for a specified period to prevent one additional adverse outcome compared with the control treatment.

An organic anion-transporting polypeptide, encoded by the SLCO1B1 gene, that mediates uptake of many drugs and endogenous compounds from blood into hepatocytes across the sinusoidal (basolateral) membrane.

The ratio of the odds of an outcome (or exposure) in one group to the odds in another group, where the odds is the probability that an event occurs divided by the probability that it does not.

The use of an authorised medicine outside the terms of its marketing authorisation, for example for an indication, age group, dose, route or duration not covered by the SmPC.

A clinical syndrome of opioid excess, mediated mainly by mu-opioid receptor agonism and defined by the triad of depressed consciousness, respiratory depression (reduced rate and/or depth) and miosis.

A medicine intended for the diagnosis, prevention or treatment of a rare, life-threatening or chronically debilitating condition, which may receive special regulatory designation and development incentives.

Drug-induced damage to the inner ear (cochlea, vestibular apparatus) or the auditory nerve, producing sensorineural hearing loss, tinnitus, or imbalance and oscillopsia.

An ATP-dependent efflux transporter (ABCB1, MDR1) that pumps a wide range of drugs out of cells, limiting their intestinal absorption and brain entry and promoting their biliary and renal excretion.

The probability, assuming the null hypothesis is true, of obtaining a result at least as extreme as the one observed; small values indicate that the data are unlikely under the null hypothesis.

Administration of a drug by a route that bypasses the gastrointestinal tract, usually by injection or infusion (intravenous, intramuscular, subcutaneous, intradermal, intrathecal and others).

An agonist that, even when occupying all available receptors, produces a maximal response smaller than that of a full agonist; its intrinsic activity lies between 0 and 1.

The leaflet enclosed in a medicine's package that gives patients approved, plain-language information on what the medicine is used for and how to use it safely.

Terms used in drug interaction analysis for the drug that causes an interaction (perpetrator or precipitant) and the drug whose concentrations or effects it alters (victim or object).

An interaction in which one drug modifies the response to another at the same or related receptors, physiological systems or pathways, independently of any change in plasma concentrations.

The branch of pharmacology that studies what a drug does to the body: the biochemical and physiological effects of drugs, their mechanisms of action and the relationship between drug concentration and response.

The study of how inherited genetic variation affects an individual's response to drugs, used clinically to guide drug and dose selection.

The study of medicinal substances of natural origin, mainly from plants but also from fungi, microorganisms and animals, including their identification, chemistry, biological activity and quality control.

An interaction in which one drug alters the absorption, distribution, metabolism or excretion of another, so that the concentrations of the affected drug change rather than its concentration–effect relationship.

The branch of pharmacology that describes what the body does to a drug: the time course of its absorption, distribution, metabolism and excretion (ADME) and the resulting concentrations in plasma and tissues.

Pharmacology means the science of the drugs

The treatment or prevention of disease by means of drugs, as distinct from surgical, physical, psychological or other non-drug interventions.

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem (WHO definition).

The first stage of testing an investigational drug in humans, usually in a small number of healthy volunteers, designed mainly to assess safety, tolerability, pharmacokinetics and, where possible, pharmacodynamics.

Functionalization reactions, mainly oxidation, reduction and hydrolysis, that introduce or unmask a polar group such as –OH, –NH2 or –COOH on a drug molecule.

The stage of clinical development in which an investigational drug is first given to patients with the target condition to obtain preliminary evidence of efficacy, explore the dose–response relationship and further characterize safety.

Conjugation reactions in which an endogenous moiety such as glucuronic acid, sulfate, glutathione, an acetyl or a methyl group is attached to a drug or to its phase I metabolite.

A large, usually randomized and controlled confirmatory study in patients that establishes the efficacy and safety of a drug at the intended dose and provides the pivotal evidence for marketing authorization.

A study conducted after a medicine has received marketing authorization to gather further information on its safety, effectiveness and optimal use, or on its use in populations and settings not studied before approval.

Opposition between two drugs that act on different receptors or pathways to produce opposing physiological effects, so that each counteracts the other's action.

A pharmacologically inert substance or sham procedure made indistinguishable from an active treatment, used mainly as a control in clinical trials.

The reversible binding of a drug to plasma proteins, chiefly albumin for acidic drugs and α1-acid glycoprotein for basic drugs, which determines the fraction of drug that is free to distribute and act.

The concurrent use of multiple medicines by one patient, most often defined as five or more regular medicines, which may be appropriate or problematic.

A CPIC phenotype for a person carrying two non-functional (no-function) alleles of a drug-metabolising enzyme gene, resulting in little or no enzyme activity.

The study of the sources and magnitude of variability in drug concentrations among individuals in a target patient population, using data pooled from many patients, often with only a few samples each.

The branch of pharmacology and prescribing concerned with dosage: the amount of drug and the frequency, route, timing and duration of administration required for a given patient and indication.

The amount or concentration of a drug needed to produce an effect of a given intensity, usually expressed as the EC50 or ED50; the lower the value, the more potent the drug.

A medicine whose risks outweigh its expected benefits in a particular patient or population, typically older adults, especially when a safer or more effective alternative exists.

An interaction in which a drug that lacks the relevant effect on its own increases the effect of another drug, through either a pharmacokinetic or a pharmacodynamic mechanism.

Laboratory and animal investigation of a drug candidate's pharmacology, pharmacokinetics and toxicity, carried out before first administration to humans to justify and design safe clinical trials.

The main outcome measure prespecified in a trial protocol to answer the principal research question, on which the sample size calculation and the main conclusion of the trial are based.

A pharmacologically inactive or weakly active compound that is converted in the body, enzymatically or chemically, into the active drug.

Lengthening of the heart-rate-corrected QT interval (QTc) on the ECG, reflecting delayed ventricular repolarization, which predisposes to torsades de pointes when marked.

A prospective experimental study in which participants are allocated by chance to an intervention or a control (placebo, usual care or an active comparator) and followed up to compare outcomes.

The return of the condition being treated, at an intensity exceeding pre-treatment levels, after a drug is stopped or its dose is rapidly reduced.

A macromolecule, usually a protein, to which a drug or endogenous ligand binds specifically and thereby initiates a change in cell function that produces a biological response.

A decrease in the number of receptors available at the cell surface or in the cell, typically in response to prolonged or excessive agonist stimulation, which reduces tissue responsiveness.

An increase in the number or sensitivity of receptors, typically after prolonged receptor blockade or reduced exposure to the endogenous agonist (e.g. denervation), leading to tissue supersensitivity.

The originally authorized medicinal product, approved on the basis of a complete dossier, against which generic or biosimilar versions are compared to demonstrate equivalence or similarity.

The ratio of the risk (cumulative incidence) of an outcome in an exposed or treated group to the risk in an unexposed or control group over the same period.

The proportional reduction in the risk of an outcome in a treated group compared with a control group, calculated as the absolute risk reduction divided by the control event rate.

The component of total clearance attributable to the kidneys: the volume of plasma cleared of drug by urinary excretion per unit time.

The modification of the dose or dosing interval of a drug that is cleared, or has active or toxic metabolites cleared, by the kidneys, to prevent accumulation and toxicity in renal impairment.

The path by which a drug is brought into contact with the body, such as oral, sublingual, rectal, intravenous, intramuscular, subcutaneous, inhaled, topical or transdermal.

Information from one or more sources suggesting a new potentially causal association, or a new aspect of a known association, between a medicine and an event, judged sufficient to justify verification.

A form of an ionisable drug substance combined with a pharmaceutically acceptable counterion, such as hydrochloride, sodium, maleate or mesilate, chosen to improve solubility, stability, crystallinity or manufacturability.

A small intracellular signalling molecule or ion, such as cAMP, cGMP, IP3, diacylglycerol or Ca²⁺, whose concentration changes in response to receptor activation and which relays and amplifies the signal inside the cell.

The degree to which a drug acts on a particular target (receptor subtype, enzyme or tissue) rather than on others, usually expressed as the ratio of its affinities or potencies at different targets.

An adverse event that results in death, is life-threatening, requires or prolongs hospitalisation, causes persistent or significant disability, is a congenital anomaly, or is otherwise medically important.

A potentially life-threatening drug-induced toxidrome caused by excess serotonergic activity in the central and peripheral nervous systems, typically after combining serotonergic drugs or after overdose.

The period during which a medicinal product, stored under the specified conditions, is expected to remain within its approved quality specifications for identity, strength, purity and performance.

An unintended effect of a medicine, occurring at normal doses, that arises from its pharmacological properties and may be harmful, neutral or occasionally beneficial.

A phenotype defined by reduced N-acetyltransferase 2 (NAT2) activity, causing slower inactivation of drugs cleared by acetylation and greater exposure at standard doses.

The maximum amount of a substance that dissolves in a given volume of solvent at equilibrium under specified conditions of temperature, pH and medium composition.

Receptors in excess of those needed to produce a maximal response, so that a full agonist can elicit its maximal effect while occupying only a fraction of the available receptors.

The unsolicited submission of reports of suspected adverse drug reactions, mainly by healthcare professionals and patients, to a national pharmacovigilance centre or to the marketing authorisation holder.

A standardised naming system for a specific haplotype of a pharmacogenetically important gene, denoted by an asterisk followed by a number, such as CYP2D6*4.

The constant plasma drug concentration achieved when the rate of drug administration equals the rate of elimination during repeated dosing.

A rare, severe, usually drug-induced mucocutaneous reaction with widespread keratinocyte death, blistering and mucosal erosions, in which epidermal detachment involves less than 10% of body surface area.

Administration of a drug under the tongue, where it dissolves and is absorbed through the oral mucosa directly into the systemic venous circulation, bypassing hepatic first-pass metabolism.

The regulator-approved document that sets out the properties and authorized conditions of use of a medicinal product for healthcare professionals, forming the legal basis of its prescribing information.

A laboratory measurement or physical sign used as a substitute for a clinically meaningful outcome (how a patient feels, functions or survives) and expected to predict the effect of therapy on that outcome.

An interaction in which two drugs that each produce a given effect on their own cause a combined effect greater than that predicted from their individual effects under additivity.

A review that uses explicit, prespecified and reproducible methods to identify, select, critically appraise and synthesize all relevant studies addressing a clearly formulated question.

A rapidly developing decrease in response to a drug after repeated doses over a short period (minutes to hours), which often cannot be overcome by increasing the dose.

The gradual, planned reduction of a drug's dose over time before stopping it, to avoid withdrawal symptoms, rebound, disease flare or insufficient endogenous hormone production.

The capacity of a drug or other agent to cause structural malformations or functional abnormalities in the embryo or fetus when exposure occurs during pregnancy.

The measurement of drug concentrations in blood at defined times, interpreted in the clinical context, to individualise dosing so as to maximise efficacy and minimise toxicity.

The unintended concurrent use of two or more drugs with the same active ingredient, the same pharmacological class or overlapping mechanisms for the same indication, without added benefit.

A measure of a drug's relative safety, classically the ratio of the dose producing toxicity (TD50) or death (LD50) in 50% of subjects to the dose producing the desired effect in 50% (ED50).

The range of doses or, more usually, plasma concentrations between the minimum effective concentration and the concentration at which unacceptable toxicity appears, within which most patients benefit safely.

The time after dosing at which the maximum plasma concentration (Cmax) is observed; an index of the rate of drug absorption.

A gradual reduction in response to a drug with repeated or continuous exposure, so that a higher dose is needed to reproduce the original effect; it develops over days to weeks.

The capacity of a substance to cause harmful effects in a living organism, or the harmful effect itself; it depends on dose, route, duration of exposure and the susceptibility of the exposed individual.

The science that studies the adverse effects of chemical, physical or biological agents on living organisms, including their mechanisms, detection, risk assessment and the management of poisoning.

A constellation of signs and symptoms (vital signs, mental status, pupils, skin and bowel sounds) characteristic of poisoning by a particular class of agents, used to identify the likely cause at the bedside.

Two enzymes whose genetic deficiency reduces inactivation of thiopurine drugs, causing excess active metabolite accumulation and a markedly increased risk of severe myelosuppression.

Delivery of a drug through intact skin into the systemic circulation, usually from an adhesive patch designed to release the drug at a controlled rate over one to several days.

The lowest drug concentration reached during a dosing interval, measured in practice immediately before the next dose, usually at steady state.

An adverse drug reaction resulting from an exaggeration of a drug's known pharmacological action; it is dose-related, predictable and usually common but rarely fatal.

An adverse drug reaction that is not expected from the drug's known pharmacology, is largely independent of dose, and is uncommon but frequently serious.

A CPIC phenotype for a person with increased drug-metabolising enzyme activity, often from a gene duplication or an increased-function allele, above the normal metabolizer range.

The proportion of the total plasma drug concentration that is not bound to plasma proteins, expressed as a fraction (0–1) or percentage; only this free drug can cross membranes and interact with receptors.

The gene encoding vitamin K epoxide reductase complex subunit 1, the pharmacological target of warfarin, whose promoter variants alter warfarin dose requirement.

A theoretical volume that describes the extent to which a drug is distributed throughout the body tissues relative to the plasma, indicating how much the drug leaves the bloodstream to enter tissues.

A characteristic cluster of signs and symptoms that follows abrupt discontinuation, rapid dose reduction or antagonist reversal of a drug to which the body has adapted during prolonged use.

A chemical that is foreign to an organism, being neither produced by it nor part of its normal biochemistry; drugs, environmental pollutants, food additives and many plant toxins are examples.

A pharmacokinetic process where the rate of drug elimination (or absorption) is constant and independent of the drug's concentration, often seen with high doses or saturated metabolism.