KINETICS - M1.1

Biopharmaceutics

is an area of study that deals with the factors influencing the bioavailability of a drug in humans and animals and the use of this information to optimize therapeutic activity of drug products.

rate and extent

Specifically, Biopharmaceutics focuses on the interrelationship of the physicochemical properties of the drug, the dosage form (drug product) in which the drug is given, and the route of administration on the ______ and ______ of systemic drug absorption.

Design, Stability, Manufacture, Release, Dissolution Rate, Delivery

Biopharmaceutics involves factors that influence __________ (6)

DRUGS

These are substances intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.

Local Effect

Obtained when the drug product is administered at the site where the pharmacological response is desired either by adsorption or penetration

Systemic Effect

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 several organs-regardless of the site and route of administration

Dosage form (drug product)

These drug delivery systems that release and deliver drug to the site of action such that they produce the desired therapeutic effect. In addition, these are designed specifically to meet the patient's needs including palatability, convenience, and safety.

Xenobiotics

Foreign compounds exposed to the biological system

DRUG PRODUCT PERFORMANCE

It is defined as the release of the drug substance from the drug product either for local drug action or for drug absorption into the plasma for systemic therapeutic activity.

Biopharmaceutics

Provides the scientific basis for drug product design and drug product performance

Physicochemical properties of the drug (PC), Dosage form (DF), Route of Administration (RoA)

Three factors that affect the bioavailability of the drug

Bioavailability

refers to the measure of systemic availability of a drug.

Bioavailability

It describes 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.

Bioavailability

In short, the term described the rate and extent of drug input.

Liberation; absorption

Drug input processes involved the _______ of the drug from its formulation matrix and __________ of the drug released from the drug product of dosage form.

Liberation

It is the release of the drug from its dosage form

Absorption

It is the process of uptake of the compound from the site of administration into the systemic circulation

BIOEQUIVALENCE

The term refers to the comparison of bioavailabilities of different formulations, drug products, or batches of the same drug product.

Pharmacokinetics

It is the science of the kinetics of drug absorption, distribution, and elimination (ie, metabolism and excretion).

Liberation and Absorption

Two steps of the Drug Input Process

Liberation

The release of the drug from its dosage form

Absorption

The movement of drug from the site of administration to the blood circulation

Absorption

It is the process of uptake of the compound from the site of administration into the systemic circulation

Distribution, Metabolism, Excretion

Three steps of the Drug Output Process

Drug Disposition

A term used to describe drug distribution and elimination

Drug disposition

It is the term used to describe drug distribution and elimination (which covers metabolism and excretion).

Drug disposition

It refers to the loss of drug from the central compartment due to transfer into other compartments and/or elimination and metabolism.

drug output

Drug disposition is also referred to as the __________ process.

Distribution, Metabolism and Excretion

Drug output processes are _______ (3)

Drug Disposition characterization

This is an important prerequisite for determination or modification of dosing regimens for individuals and groups of patient

Distribution

The process by which drug diffuses or is transferred from intravascular space to extravascular space (body tissues)

Distribution

It is the partitioning of drug molecules among numerous locations in the body

Elimination

Refers to the irreversible removal of drug from the body by all routes of elimination (metabolism and excretion)

Decline

Drug elimination results to (increase/decline) in plasma drug concentration observed after systemic drug absorption

Metabolism

Process by which the drug is chemically converted in the body to a metabolite, usually through an enzymatic process

Biotransformation

Other term for metabolism

Excretion

Removal of intact drug

renal excretion

Non-volatile drugs are excreted mainly by _________

Experimental approach

An approach of pharmacokinetic studies in which it includes: (1) Development of biologic sampling techniques; (2) Analytical methods for the measurement of drugs and metabolites; and (3) Procedures that facilitate data collection and manipulation

Theoretical approach

An approach of pharmacokinetic studies in which it includes development of pharmacokinetic models that predict drug disposition after drug administration

Clinical pharmacokinetics

It is the application of pharmacokinetic methods to drug therapy in patient care.

Clinical pharmacokinetics

It involves multidisciplinary approach to individually optimized dosing strategies based on the patient's disease state and patient-specific considerations

Population pharmacokinetics

refers to the study of pharmacokinetic differences of drugs in various population groups.

Pharmacodynamics

It is the study of the biochemical and physiological effects of drugs on the body. This includes the mechanisms of drug action and the relationship between drug concentration and effect.

Pharmacodynamics

It is how a drug interacts quantitatively with a drug receptor to produce a response (effect).

Pharmacodynamics

Refers to the relationship between the drug concentration at the site of action (receptor) and pharmacologic response, including biochemical and physiologic effects that influence the interaction of drug with the receptor

Drug-receptor interaction

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

Pharmacokinetic-pharmacodynamic models

Constructed to relate plasma drug level to drug concentration at the site of action and establish the intensity and time course of the drug

Receptors

These are the molecules that interact with specific drugs to produce a pharmacological effect in the body.

Drug exposure

Refers to the dose (drug input to the body) and various measures of acute or integrated drug concentrations in plasma and other biological fluid

Drug response

Refers to direct measure of the pharmacologic effect of the drug

Toxicokinetics

It refers to the application of pharmacokinetic principles to the design, conduct, and interpretation of drug safety evaluation studies and in validating dose-related exposure in animals. (eg., preclinical drug development)

Toxicokinetics

The data obtained in the study of such aids in the interpretation of toxicologic findings in animals and extrapolation of the resulting data to humans

Pre-clinical

Toxicokinetic studies are performed in animals during (pre-clinical/post-clinical) drug development and may continue after the drug has been tested in clinical trials.

Clinical toxicology

It is the study of adverse effects of drugs and toxic substances (poisons) in the body.

Whole blood

[Blood Sample Type] Obtained by Venous puncture and contains an anticoagulant such as heparin or EDTA

Whole blood

[Blood Sample Type] Contains all the cellular and protein elements of blood

Serum

[Blood Sample Type] Obtained from Whole blood after the blood is allowed to clot and the clot is removed

Serum

[Blood Sample Type] It does not contain the cellular elements, fibrinogen, or the other clotting factors from the blood

Plasma

[Blood Sample Type] The liquid supernatant obtained after centrifugation of non-clotted whole blood that contains an anticoagulant (heparin)

Plasma

[Blood Sample Type] It is the noncellular fraction of whole blood and contains all the proteins including albumin

Tissue drug concentrations

Plasma perfuses all the tissues of the body, including the cellular elements in the blood. Thus, changes in the drug concentration in plasma will reflect changes in ________ drug concentrations

Tissue punch biopsy

Drug concentration in tissues is used to ascertain if the drug reached the tissues and reached the proper concentration within the tissue. A method to determine drug concentration in tissues is _____________

Urine

an indirect method to ascertain the bioavailability of a drug

Urine

the rate and extent of drug excreted in the _______ reflects the rate and extent of systemic drug absorption

Feces

May reflect drug that has not been absorbed after an oral dose

Feces

May reflect drug that has been expelled by biliary secretion after systemic absorption

Fecal collection

___________ is performed to recover certain solid oral dosage forms that do not dissolve in the gastrointestinal tract but slowly leach out drug

Saliva

Drug levels in the _________ tend to approximate free drug because only free drug diffuses into the __________

pKa of drug; pH of saliva

Saliva/plasma drug concentration ratio is mostly influenced by the ______ of the drug and the _______ of the saliva

Plasma level - time curve

Generated by obtaining the drug concentration in plasma samples taken at various time intervals after a drug product is administered

Minimum Effective Concentration

reflects the minimum concentration of drug needed at the receptors to produce the desired pharmacologic effect

Minimum Toxic Concentration

represents the drug concentration needed to just barely produce a toxic effect

Duration of action

the difference between the onset time and the time for the drug to decline back to the MEC

Intensity (of pharmacologic effect)

It is proportional to the number of drug receptors occupied, which is reflected in the observation that higher plasma drug concentrations produce a greater pharmacologic response, up to a maximum

Onset time

The time required for the drug to reach the MEC.

Peak plasma level

related to the dose, the rate constant for absorption, and the elimination constant of the drug

maximum drug concentration

Peak plasma level is also known as

Time for peak plasma level

time of maximum drug concentration in the plasma

Time for peak plasma level

a rough marker of average rate of drug absorption

Area under the curve (AUC)

related to the amount of drug absorbed systemically

Time, Dose, and Route of Administration

Needed Pharmacokinetic information to deem plasma drug levels useful for dosage adjustment

Drug therapy regimen

Estimation of drug dosing ¨ Prediction of the time course of drug efficacy for a given dose

Pharmacodynamic

The ability of the drug to reach the site of action results to its (pharmacodynamic/pharmacokinetic) properties (e.g., ability to bind with receptors or affect other targets for drug action) which is the RESPONSE.

Models

A hypothesis using mathematical terms to describe quantitative relationships concisely

Pharmacokinetic parameter

a constant for the drug that is estimated from the experimental data (k - elimination rate constant)

Empirical models

[Types of Models] Simply interpolates the data

Empirical models

[Types of Models] Allows an empirical formula to estimate drug level over time (only when limited information is available)

Empirical models

[Types of Models] Practical but NOT USEFUL in explaining the mechanism of the actual process by which the drug is absorbed, distributed, and eliminated

Physiologically based model

[Types of Models] Also known as Blood flow or perfusion models

Physiologically based model

[Types of Models] PK models based on known anatomic and physiologic data

Physiologically based model

[Types of Models] Potentially predict REALISTIC tissue drug concentrations

Physiologically based model

[Types of Models] Info required is experimentally DIFFICULT TO OBTAIN

COMPARTMENT MODEL

[Types of Models] The body is represented as a single compartment or container for some drugs.

Tissue or group of tissues

In a compartment model, compartment is NOT A REAL physiologic or anatomic region but is considered a ________ or group of _________ that have similar blood flow and drug affinity

True

True or False: In the compartment model, within each compartment, the drug is considered uniformly distributed

False (Mixing of the drug within a compartment is RAPID and HOMOGENOUS)

True or False: In the compartment model, the mixing of the drug within a compartment is rapid and heterogenous

CENTRAL COMPARTMENT

In the compartment model, highly perfused organs such as heart, liver, and lungs are called ________ compartment

PERIPHERAL COMPARTMENT

In the compartment model, poorly perfused organs such as fat tissues, muscle tissues, and CSF are called _______________ compartment

Mammillary model

[Types of Compartment Model) Most common compartment model used in pharmacokinetics