Basic concepts Flashcards
is the extent or fraction of drug absorbed upon extravascular administration in comparison to the dose size administered
Absolute bioavailability
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 rare exception is absorption by pinocytosis.
Absorption
rate constant of the entire process of drug transfer into the body, through all biological membranes.
Absorption rate constant
increase of drug concentration in blood and tissue upon multiple dosing until steady state is reached
Accumulation
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.
Apparent partition coefficient
integral of drug blood level over time from zero to infinity, and is a measure of quantity of drug absorbed and in the body.
Area under the curve
is the phenomenon that drugs emptied via bile into the small intestine can be reabsorbed from the intestinal lumen into systemic circulation
Biliary recycling/
Enterohepatic recirculation
rate and extent to which an active drug substance or moiety is absorbed from the pharmaceutical dosage form and becomes available at its site of action
Bioavailability
achieved if its extent and rate of absorption are not statistically different from those of the standard when administered at the same molar dose
Bioequivalence
requirement imposed by the FDA for in vitro and/or in vivo testing of specified drug products which must be satisfied as a condition of marketing
Bioequivalence requirement
deals with the physical & chemical properties of the drug substance, the dosage form, and the body and the biological effectiveness of a drug and/or drug products 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
Biopharmaceutics
actual site of action of a drug in the body. It is the drug-receptor interaction on the molecular level or the effect of the presence of a drug on biopolymers. The biophase may be the surface of a cell or within the cell, i.e. one of the organelles
Biophase
speed of blood perfusion in an organ, usually expressed in mL/100 g organ weight/min. Blood flow rates may differ several-fold between rest and exercise
Blood flow rate
demonstrate the concentration in blood, plasma, or serum upon administration of a dosage form by various routes of administration. Blood, plasma, or serum level curves are plots of drug concentration versus time on numeric or semilog 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
Blood, plasma, serum level
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
Central compartment
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
Clearance
an entity which can be described by a definite volume and a concentration of drug contained in that volume.
Compartment
the difference in the concentration in two phases usually separated by a membrane
Concentration gradient
are 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.
Cumulative urinary excretion curve
portion of a prolonged release dosage form which liberates the drug from the dosage form at a slower rate than its unrestricted absorption rate
Depot phase
the viscous layer of concentrated drug solution around a dissolving particle
Diffusion layer
the loss of drug from the central compartment due to distribution into other compartments and/or elimination.
Disposition
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.
Dosage regimen/
Dose rate
change of one or more of the pharmacokinetic processes of absorption, distribution, metabolism, & excretion with increasing dose size
Dose dependency
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
Dose dumping
amount of drug in µg, mg, units
Dose size
time period between administration of maintenance doses
Dosing interval
chemical compound of synthetic, semisynthetic, natural, or biological origin which interacts with human or animal cells
Drug
pharmacologically active compounds undergoing evaluation of their potential as future drug substances
Drug candidates
gross pharmaceutical form containing the active pharmaceutical ingredient (s) and vehicle substances necessary in formulating a medicament of desired dosage, desired volume, and desired application form, ready for administration
Drug product/
Dosage form
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.
Drug release/
Liberation
drug product, usually of unvarying composition, labeled with a registered trademark of a company
Drug specialty/
Brand product
active ingredients within a dosage form
Drug substances
time in hours necessary to reduce the drug concentration in the blood, plasma or serum to one-half after equilibrium is reached.
Elimination half-life
the increase in enzyme content or rate of enzymatic processes resulting in faster metabolism of a compound.
Enzyme induction
decrease in rate of metabolism of a compound usually by competition for an enzyme system
Enzyme inhibition
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
Excretion
refers to all routes of administration except those where the drug is directly introduced into the blood stream. Examples are IM, SC, PO, Oral, Rectal, IP, Topical.
Extravascular administration
graphical method for the separation of exponents such as separating the absorption rate constant from the elimination rate constant. It is synonymous with Residual method.
Feathering
the phenomenon whereby drugs may be metabolized (not chemically degraded) following absorption but before reaching systemic circulation. Hepatic first pass effect may occur following PO and deep rectal administration. It may be avoided by using sublingual and buccal routes of administration.
First pass effect
drug product marketed under the nonproprietary or common name of the drug(s)
Generic product
hypothetical volume of distribution in mL of the unmetabolized drug which is cleared in one minute via the liver.
Hepatic clearance
portion of a prolonged release dosage form which is immediately available for absorption
Initial phase
all routes of administration where the drug is directly introduced in the blood stream such as IV, IA, IC. Its BA is 100 percent
Intravascular administration
physiologic nonsense and poor use of language. The correct term is IV Push
IV Bolus
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
LADMER system
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 PO administration due to slow disintegration and dissolution of tablets or capsules.
Lag time
series of structurally related chemical compounds that have shown interesting pharmacological activity and from which drug candidates may be selected
Leads
the dose size used in initiating therapy so as to yield therapeutic concentration which will result in clinical effectiveness.
Loading / Primary / Initial dose
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
Local effect
dose size required to maintain the clinical effectiveness or therapeutic concentration according to the dosage regimen.
Maintenance dose
sum of all the chemical reactions for biotransformation of endogenous and exogenous substances which take place in the living cell.
Metabolism
sum of all body regions to which a drug eventually distributes, but is not in instantaneous equilibrium.
Peripheral compartment
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
Pharmaceutical alternatives
drug products that contain identical amounts of the active pharmaceutical 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
Pharmaceutical equivalence
deals with the changes of drug concentration in the drug product and changes of concentration of a drug and/or its metabolites in the human or animal body following administration
Pharmacokinetics
occurs when the drug combines with plasma protein to form a reversible complex
Protein binding
process with the slowest rate constant in a system of simultaneous kinetic process
Rate-limiting step
site in the biophase to which drug molecules can be bound. A receptor (substrate) is usually a protein or proteinaceous material
Receptor
the extent of drug absorbed upon extravascular administration in comparison to the dose size of a standard administered by the same route.
Relative bioavailability
method of representing experimental data describing exponential processes that allow them to be presented in linear form
Semi-logarithmic plot
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 the skin or mucosa by reducing the barrier resistance
Sorption promoters / permeation enhancers
level of drug accumulation in blood and tissue upon multiple dosing when input and output are at equilibrium.
Steady state
those whose pharmacological action is not directly dependent on chemical structure. They have no functional group, are highly lipophilic, and do not react easily. They act by physicochemical processes. Examples include ether, nitrous oxide, halothane, phenol, ethyl alcohol, octyl alcohol, and acetone
Structural nonspecific drugs
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 antibiotics, sulfonamides, glycosides, alkaloids, etc.
Structural specific drugs
property of prolonged release dosage forms where the liberation (drug release) rate constant is smaller than the unrestricted absorption rate constant
Sustained release
obtained when the drug released from the drug product enters the bloodstream and/or lymphatic stream and is distributed within the body – or at least in several organs – regardless of the site and route of administration
Systemic effect
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.
Unit membrane
phenomenon that occurs when drugs filtered through the glomeruli are reabsorbed from the tubuli into systemic circulation
Urinary cycling
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.
Vehicle substances
hypothetical volume of body fluid that would be required to dissolve amount of drug at the same concentration as that found in the blood.
Volume of distribution
