Chapter 1: Definition of Terms

Question 1

deals with the physical and chemical properties of the drug substance, the dosage form, and the body and the biological effectiveness of a drug and/or drug product upon administration, i.e., the drug availability to the human or animal body from a given dosage form, considered as a drug delivery system. The time course of the drug in the body and the quantifying of the drug concentration pattern are explained by pharmacokinetics

Answer 1

Biopharmaceutics

Question 2

deals with the changes of drug concentration in the drug product and changes of concentration of a drug and/or its metabolite(s) in the human or animal body following administration, i.e., the changes of drug concentration in the different body fluids and tissues in the dynamic system of liberation, absorption, distribution, body storage, binding, metabolism, and excretion

Answer 2

Pharmacokinetics

Question 3

the application of pharmacokinetic principles in the safe and effective treatment of individual patients, and in the optimization of drug therapy

Answer 3

Clinical Pharmacokinetics

Question 4

uses equations to characterize certain phenomena such as protein binding, adsorption, and nonlinear or saturation processes often observed with increasing dose sizes

Answer 4

Michaelis-Menten Kinetics

Question 5

refers to a change of one or more of the pharmacokinetic parameters during absorption, distribution, metabolism and excretion by saturation or overloading of processes due to increased dose sizes

Answer 5

Nonlinear Kinetics or Saturation Kinetics

Question 6

the study of pharmacokinetic drug parameters as affected by circadian rhythm or diurnal variation

Answer 6

Chrono pharmacokinetics

Question 7

is the biological clock controlling rhythms of processes during a twenty-four hour cycle which is based on endogenous factors

Answer 7

Circadian Rhythm

Question 8

the biological clock controlling rhythms of processes during a twenty-four hour cycle which is based on external synchronizers (Zeitgeber)

Answer 8

Diurnal Variation

Question 9

the integral of drug blood level over time from zero to infinity, and is a measure of quantity of drug absorbed and in the body

Answer 9

Area Under the Curve

Question 10

mathematically defined by AUMC = ∫ 0∞ tCdt, i.e., it is the area under the curve observed for the product of time and concentration versus time

Answer 10

Area Under First Statistical Moment Curve

Question 11

demonstrate the concentration in blood, plasma or serum upon administration of a dosage form by various routes of administration.

Answer 11

Blood-, Plasma- or Serum-Levels

Question 12

plots of drug concentration versus time on numeric or semi-log graph paper. Blood-, plasma- or serum-levels are obtained from blood samples by venipuncture in certain time intervals after administration of the drug product and chemical or microbiological analysis of the drug in the biological fluid

Answer 12

Blood-, plasma- or serum-level curves

Question 13

plots of the actual cumulative amounts of drug and/or its metabolites excreted into urine versus time upon administration of a drug product by various routes of administration

Answer 13

Cumulative Urinary Excretion Curves

Question 14

the ratio of the concentrations at equilibrium between a lipid phase (usually n-octanol) and an aqueous phase (usually buffer pH 7.4). The apparent partition coefficient is uncorrected for dissociation or association in either phase

Answer 14

Apparent Partition Coefficient

Question 15

are composite rate constants consisting of two or more micro constants. a and ẞ are hybrid rate constants

Answer 15

Hybrid Rate Constants

Question 16

are those constants which are part of the hybrid constants. Micro constants are for instance k12, k21, k13

Answer 16

Micro Constants

Question 17

refers to a graphical method for the separation of exponents such as separating the absorption rate constant from the elimination rate constant, or the a-slope from the ẞ-slope, or the absorption rate constant from the a-rate constant.

Answer 17

Feathering

Question 18

the process with the slowest rate constant in a system of simultaneous kinetic processes

Answer 18

Rate Limiting Step

Question 19

is not a “real” volume but an artifact – a hypothetical volume of body fluid that would be required to dissolve the total amount of drug at the same concentration as that found in the blood. It is a proportionally constant relating the amount of drug in the body to the measured concentration in biological fluid (blood, plasma or serum)

Answer 19

Volume of Distribution

Question 20

the time in hours necessary to reduce the drug concentration in the blood, plasma or serum to one-half after equilibrium is reached. The elimination half-life may be influenced by: dose size, variation in urinary excretion (pH), intrasubject variation, age, protein binding, other drugs and diseases (especially renal and liver diseases). Loss of drug from the body, as described by the elimination half-life, means the elimination of the administered parent drug molecule (not its metabolites) by urinary excretion, metabolism or other pathways of elimination (lung, skin, etc.)

Answer 20

Elimination Half-Life of a drug

Question 21

refers to all routes of administration except those where the drug is directly introduced into the blood stream. Extravascular routes are: I.M., S.C., P.O., Oral, Rectal, I.P., Topical, etc.

Answer 21

Extravascular Administration

Question 22

refers to all routes of administration where the drug is directly introduced into the blood stream, i.e., I.V., Intraarterial, and Intracardiac; bioavailability 100 percent, f = 1

Answer 22

Intravascular Administration

Question 23

includes buccal, sublingual and perlingual administration routes where the drug is absorbed from the mouth cavity (no first-pass effect)

Answer 23

Oral Administration

Question 24

indicates that the dosage form is swallowed and the drug is absorbed from the GI-tract (first-pass effect possible)

Answer 24

Peroral Administration

Question 25

occurs when the next dose of the same drug is administered only after the drug of the previous dose is completely eliminated from the body

Answer 25

Single Dose Administration

Question 26

is when a drug is given repeatedly at intervals shorter than those required to completely eliminate the drug of the previously given dose

Answer 26

Multiple Dose Administration

Question 27

is the increase of drug concentration in blood and tissue upon multiple dosing until steady state is reached

Answer 27

Accumulation

Question 28

is a level of drug accumulation in blood and tissue upon multiple dosing when input and output are at equilibrium. The steady state drug concentrations fluctuate (oscillate) between a maximum and a minimum steady state concentration within each dosing interval

Answer 28

Steady State

Question 29

is the maintenance of a steady state which characterizes the internal environment of the healthy organism. An important function of homeostasis is the regulation of the fluid medium and volume of the cell

Answer 29

Homeostasis

Question 30

is the period of time which elapses between the time of administration and the time a measurable drug concentration is found in blood, Lag times are often found upon P.O: administration due to slow disintegration and dissolution of 1 tablets or capsules

Answer 30

Lag Time

Question 31

is the time when 63.2 percent of an intravenous dose has been eliminated from the pharmacokinetic system

Answer 31

Mean Transit or Residence Time

Question 32

is the difference in the concentration in two phases usually separated by a membrane

Answer 32

Concentration Gradient

Question 33

is the viscous layer of concentrated drug solution around a dissolving particle

Answer 33

Diffusion Layer

Question 34

is defined as both the relative amount of drug from an administered dosage form which enters the systemic circulation and the rate at which the drug appears in the blood stream

Answer 34

Bioavailability

Question 35

is the extent or fraction of drug absorbed upon extravascular administration in comparison to the dose size administered

Answer 35

Absolute Bioavailability

Question 36

is the extent of drug absorbed upon extravascular administration in comparison to the dose size of a standard administered by the same route

Answer 36

Relative Bioavailability

Question 37

deals with the complex dynamic processes of liberation of an active ingredient from the dosage form, its absorption into systemic circulation, its distribution and metabolism in the body, the excretion of the drug from the body and the achievement of response

Answer 37

LADMER-System

Question 38

is the delivery of the active ingredient from a dosage form into solution. The dissolution medium is either a biological fluid or an artificial test fluid (in vitro). Drug release is characterized by the speed. (liberation rate constant) and the amount of drug appearing in solution.

Answer 38

Drug Release or Liberation

Question 39

is the process of uptake of the compound from the site of administration into the systemic circulation. A prerequisite for absorption is that the drug be in aqueous solution. The only relatively rare exception is absorption by pinocytosis

Answer 39

Absorption of drugs

Question 40

the sum of all the chemical reactions for biotransformation of endogenous and exogenous substances which take place in the living cell

Answer 40

Metabolism

Question 41

the final elimination from the body's systemic circulation via the kidney into urine, via bile and saliva into intestines and into feces, via sweat, via skin and via milk

Answer 41

Excretion of drugs

Question 42

the increase in enzyme content or rate of enzymatic processes resulting in faster metabolism of a compound. If a drug stimulates its own metabolism, it is called auto-induction, and, if it is caused by other compounds, it is called foreign-induction

Answer 42

Enzyme Induction

Question 43

the decrease in rate of metabolism of a compound usually by competition for, an enzyme system

Answer 43

Enzyme Inhibition

Question 44

describes the phenomenon whereby drugs may be metabolized (not chemically degraded) following absorption but before reaching systemic circulation. Hepatic first-pass effect may occur following P.O. and deep rectal administration. It may be avoided by using sublingual and buccal routes of administration. Pulmonary first-pass effect cannot be avoided by intravenous, buccal or sublingual routes

Answer 44

First-Pass Effect

Question 45

is a part of the alimentary canal comprising stomach, small intestine and large intestine

Answer 45

Gastrointestinal Tract

Question 46

is the phenomenon observed if the rate of absorption is slower than the rate of elimination, or if one of the distribution rates is slower than the rate of elimination

Answer 46

Flip-Flop Model

Question 47

is the actual site of action of drugs in the body. It is the drug-receptor interaction on molecular level or the influence of biopolymers by the presence of drug. The biophase may be the surface of a cell or within the cell, i.e., one of the organelles

Answer 47

Biophase

Question 48

is the combining of a drug molecule with the receptor for which it has affinity, and the initiation of a pharmacologic response by its intrinsic activity

Answer 48

Drug-Receptor Interaction

Question 49

is a site in the biophase to which drug molecules can be bound. A receptor ( = substrate) is usually a protein or proteinaceous material

Answer 49

Receptor

Question 50

is the phenomenon which occurs when a drug combines with plasma protein (particularly albumin) or tissue protein to form a reversible complex. Protein binding is usually non-specific and depends on the drug's affinity to the protein molecule, the number of protein binding sites, protein and drug concentration. Drugs can be displaced from protein binding by other compounds having higher affinity for the binding sites

Answer 50

Protein Binding

Question 51

is the physical barrier to transport in the body. It is lipoidal in nature and consists of a double row of phospholipids sandwiched between one layer each of protein

Answer 51

Unit Membrane

Question 52

in pharmacokinetics is an entity which can be described by a definite volume and a concentration of drug contained in that volume. In pharmacokinetics, experimental data are explained by fitting them to compartment models

Answer 52

Compartment

Question 53

is the sum of all body regions (organs and tissue) in which the drug concentration is in instantaneous equilibrium with that in blood or plasma. The blood or plasma is always part of the central compartment

Answer 53

Central Compartment

Question 54

is the sum of all body regions (i.e., organs, tissues or parts of it) to which a drug eventually distributes, but is not in instantaneous equilibrium. The peripheral compartment is sometimes further subdivided into a Shallow and a Deep Compartment

Answer 54

Peripheral Compartment

Question 55

is the loss of drug from the central compartment due to transfer (distribution) into other compartments and/or elimination and metabolism

Answer 55

Disposition

Question 56

is the hypothetical volume of distribution in ml of the unmetabolized drug which is cleared per unit of time (ml/min or ml/h) by any pathway of drug removal (renal, hepatic and other pathways of elimination)

Answer 56

Clearance

Question 57

is the theoretical unrestricted maximum clearance of unbound drug by an eliminating organ

Answer 57

Intrinsic Clearance

Question 58

is the ratio of creatinine excreted in urine to the concentration of creatinine in plasma. The creatinine clearance decreases with renal impairment and with age

Answer 58

Creatinine Clearance

Question 59

is the hypothetical volume of distribution in ml of the unmetabolized drug which is cleared in one minute via the liver

Answer 59

Hepatic Clearance

Question 60

is the hypothetical plasma volume in ml (volume of distribution) of the unmetabolized drug which is cleared in one minute via the kidney

Answer 60

Renal Clearance

Question 61

describes the clearance of the hypothetical plasma volume in ml (volume of distribution) of a drug per unit time due to excretion via kidney, liver, lung, skin, etc. and metabolism

Answer 61

Total Clearance

Question 62

is the phenomenon that drugs emptied via bile into the small intestine can be reabsorbed from the intestinal lumen into systemic circulation

Answer 62

Biliary Recycling (Enterohepatic Recirculation)

Question 63

is the phenomenon in which drugs emptied via bile into the small intestine can be reabsorbed from the intestinal lumen into systemic circulation

Answer 63

Enterohepatic Recirculation (Biliary Recycling)

Question 64

is the phenomenon that occurs when drugs filtered through the glomeruli are reabsorbed from the tubuli into systemic circulation

Answer 64

Urinary Recycling

Question 65

is obtained when the drug product is administered at the site where the pharmacological response is desired and when the drug released from the product acts by adsorption to the skin or mucosa or penetrates into the skin or mucosa, but does not enter the systemic blood circulation or lymphatic stream

Answer 65

Local Effect

Question 66

is obtained when the drug released from the drug product enters the blood and/or lymphatic streams and is distributed within the body-or at least in several organs, regardless of the site and route of administration

Answer 66

Systemic Effect

Question 67

is a chemical compound of synthetic, semisynthetic, natural or biological origin which interacts with human or animal cells. The interactions may be quantified, whereby these resulting actions are intended to prevent, to cure or to reduce ill effects in the human or animal body, or to detect disease-causing manifestations

Answer 67

Drug

Question 68

is the gross pharmaceutical form containing the active ingredient(s) [drug(s)] and vehicle substances necessary in formulating a medicament of desired dosage, desired volume and desired application form, ready for administration

Answer 68

Drug Product or Dosage Form

Question 69

is a drug product, usually of unvarying composition, labeled with a registered trade mark of a single company

Answer 69

Drug Specialty or Brand Product

Question 70

is a drug product marketed under the nonproprietary or common name of the drugs(s)

Answer 70

Generic Product

Question 71

are drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount, or dosage form or as the same salt or ester

Answer 71

Pharmaceutical Alternatives

Question 72

are drug products that contain identical amounts of the identical active drug ingredient, i.e., the same salt or ester of the same therapeutic moiety, in identical dosage forms, but not necessarily containing the same inactive ingredients

Answer 72

Pharmaceutical Equivalents

Question 73

of a drug product is achieved if its extent and rate of absorption are not statistically significantly different from those of the standard when administered at the same molar dose

Answer 73

Bioequivalence

Question 74

is a requirement imposed by the Food and Drug Administration for in vitro and/or in vivo testing of specified drug products which must be satisfied as a condition of marketing

Answer 74

Bioequivalence Requirement

Question 75

are those whose pharmacological action is not directly dependent on chemical structure. They have no functional groups, are highly lipophilic and do not react, easily. They act by physico-chemical processes. Examples include: ether, nitrous oxide, halothane, phenol, ethyl alcohol, octyl alcohol, acetone

Answer 75

Structural Nonspecific Drugs

Question 76

are those whose pharmacological action results primarily from their chemical structure. They have functional groups, and combine to the three-dimensional structure of receptors in the biophase. Examples include anti- biotics, sulfonamides, glycosides, alkaloids, etc.

Answer 76

Structural Specific Drugs

Question 77

is the property of prolonged release dosage forms where the liberation (drug release) rate constant is smaller than the unrestricted absorption rate constant

Answer 77

Sustained Release

Question 78

is that portion of a prolonged release dosage form which liberates the drug from the dosage form at a slower rate than its unrestricted absorption rate

Answer 78

Depot Phase

Question 79

is that portion of a prolonged release dosage form which is immediately available for absorption

Answer 79

Initial Phase

Question 80

are defined as substances that have no pharmacological properties of their own in the amount used, but which can improve the penetration of drugs into the skin or their permeation through skin or mucosa by reducing the barrier resistance

Answer 80

Sorption Promoters or Permeation Enhancers

Question 81

is the carrier of the drug in the drug product. It is composed of all necessary vehicle substances. Vehicle Substances are additives which are necessary in formulating a dosage form from the drug. The vehicle substances should be chemically inert and should not have any pharmacological effect in the dose used

Answer 81

Vehicle

Question 82

are used to produce, from a relatively small amount of drug, a dosage form of the desired strength, volume, form or consistency suitable for administration

Answer 82

Vehicle substances

Question 83

is the systematized dosage schedule for therapy, i.e., the proper dose sizes and proper dosing intervals required to produce clinical effectiveness or to maintain a therapeutic concentration in the body

Answer 83

Dosage Regimen or Dose Rate

Question 84

refers to a change of one or more of the pharmacokinetic processes of absorption, distribution, metabolism and excretion with increasing dose size

Answer 84

Dose Dependency

Question 85

is a term used to describe the achievement of sustained drug concentration by simply increasing the dose size or by accidental fast release of drug from a sustained release dosage form

Answer 85

Dose Dumping

Question 86

is the graphical presentation of the pharmacological or clinical effectiveness or toxicity (response) versus dose. A log dose-response curve is sigmoid with a straight-line middle section; a log dose-probability curve results in an entirely straight line

Answer 86

Dose-Response Curve

Question 87

is the amount of drug in μg (=mcg), mg, units or other dimensions to be administered

Answer 87

Dose Size

Question 88

is the time period between administration of maintenance doses

Answer 88

Dosing Interval

Question 89

is the dose size used in initiating therapy so as to yield therapeutic concentration which will result in clinical effectiveness

Answer 89

Loading Dose, Priming Dose or Initial Dose

Question 90

is the dose size required to maintain the clinical effectiveness or therapeutic concentration according to the dosage regimen

Answer 90

Maintenance Dose

Question 91

is a physiologic nonsense and poor use (misuse) of language. A bolus (Greek: bolos) is a bite, something solid which is swallowed and is then absorbed from the intestines. The correct term would be I.V. Push

Answer 91

I.V. Bolus

Question 92

is the speed of blood perfusion in an organ, usually expressed in ml/100g organ weight/min. Blood flow rates may differ several-fold between rest, or immobilization, and exercise

Answer 92

Blood Flow Rate

Question 93

is the determination and recording of drug concentrations during the course of therapy in order to adjust, if necessary, the dosage regimen

Answer 93

Monitoring

Question 94

is a patient's body weight minus the fat mass. Drugs of low lipid solubility should be dosed in obese patients according to the lean body weight

Answer 94

Lean Body Weight