Introduction to Biopharmaceutics (and Pharmacokinetics)

IP 155 Laboratory

Daryl E. Kayanan

Drug in dosage form

Liberation

Drug particles in

body fluids/cavities

Dissolution

Drug in solution

Degradation

Absorption

Liver

Metabolism

Blood/Plasma

Free

Distribution

Peripheral

Tissues

Pharmacologic effect

Pharmacodynamics Biopharmaceutics

Pharmacokinetics

Drug in contact

with body’s

membranes

Bound

Elimination

Kidneys Excretion

Site of action

Biopharmaceutics

• Biopharmaceutics is the study of the

interrelationships between the physical and

chemical properties of the drug, the design

and choice of its system of drug delivery,

and the expected therapeutic response after

its administration to the patient

• Biopharmaceutics is interrelated with

Physical pharmacy

Medicinal chemistry

Pharmacokinetics

Formulation

Biopharmaceutics

• “Pharmaceutics” + “Bio” – interdependence

of biological aspects of the living system and

the physical-chemical properties that govern

the preparation and behavior of the drug

• “Liberation + Absorption”

Solubility

Salt forms

Dissolution

Bioavailability

Gastric emptying Dosage forms

Diffusion

Absorption

Route of administration Bioequivalence

Permeability

Pharmacokinetics

• Kinetics of drug absorption, distribution, and

elimination

• Deals with the time course of drug in the

body (ADME)

Drug at site of absorption

Drug is absorbed

Drug is distributed to different tissues

Drug is metabolized

Drug is excreted by the body by different means

Elimination Disposition

Drug concentration-time profile

• Characterization of the time course of a

drug inside the body

• Administration of the same dose of different

drugs to the same individual will produce

different conc-time profiles. This is because

different drugs have different absorption and

disposition characteristics

• Administration of the same dose of a drug to

different individuals will produce different

conc-time profiles as well the same drug

can be absorbed, distributed, and

eliminated at different rates in different

individuals

Pharmacokinetics

• Each process or processes combined is

associated with one or more pharmacokinetic parameters describe or determine the rate

and/or magnitude of the different processes

Examples

• Half-life (t1/2)

how long would a drug stay in the body

• Absorption rate constant (ka)

Factor that determines how fast can a drug be

absorbed at a specific site of action

• Clearance

Capability of a drug to be cleared from the bloodstream

or by an organ, which may either proceed to elimination

or distribution to other tissues

Rates and Orders of the

Pharmacokinetic Process

• The rate • Instantaneous speed at which a process occurs

(ex. Rate of drug absorption = amt absorbed per

unit time)

• The Rate Constant • Factor that determines the rate of the process

• The Order • Determines how the amount of the drug involved

will influence the rate of the process

Orders of pharmacokinetic

processes

Zero-order process

• Constant rate constant amount of drug

involved in the process

• C = Co - kt

First order process

• Constant percentage of drug involved rate is

proportional to the amount of drug involved in

the process

• ln C = ln Co - kt

Drug Absorption

Definition:

• Absorption is the rate and extent at which drugs

reach the systemic circulation from the site of

drug administration

• Thus… A drug has been “absorbed” if it has

reached the systemic circulation

• Also… Drugs directly administered into the

bloodstream are assumed to be 100% absorbed

Drug Absorption

• Drugs administered extravascularly would not

have 100% absorption. Biopharmaceutics is

concerned with the factors affecting drug

absorption, as well as factors affecting drug

liberation

2 fundamental parameters that govern drug

absorption:

• Solubility

• Permeability

Bioavailability (F)

• The fraction of drug dose of unchanged drug

that reaches the systemic circulation

• The rate and extent to which the API is absorbed

from the drug product and becomes available at

the site of action

F = Fa x Fg x Fh

Fa = fraction of drug absorbed

Fg = fraction of drug that escapes

gastrointestinal metabolism

Fh = fraction that escapes first-pass effect

Bioequivalence

• “Two drug products (same API) are

bioequivalent if after drug administration of the

same molar dose, their bioavailabilities are the

same and provide similar effects with respect to

safety and efficacy.”

• Should apply both in single or multiple

administrations

• Results in vivo reflect the biopharmaceutics of

the drug product

• The goals of generic drugs are to be

bioequivalent with the innovator drug

Pharmacokinetic basis of bioequivalence

Based on these 3 parameters:

1. Maximum drug concentration (Cpmax)

2. Time to peak (tmax)

3. AUC (AUC0→t(last) and AUC0→∞)