The substantial degradation of an orally administered drug caused by enzyme metabolism in the

liver before the drug reaches the systemic circulation.

First-pass metabolism
Disposition
Antagonist
Hydrophilic
The increase in hepatic enzyme activity that results in greater metabolism of drugs
Bioavailability
Elimination
Enzyme
Enzyme induction
The study of the factors associated with drug products and physiological processes, and the
resulting systemic concentration of drugs.
Disposition
Complexation
Biopharmaceutics
Bioavailability
The comparison of bioavailability between two dosage forms.
Bioequivalency
Bioavailability
Biopharmaceutics
Biological
The relative amount of an administered dose that reaches the general circulation and the rate at
which this occurs
Biological
Bioavailability
Biopharmaceutics
Bioequivalence
Water repelling; cannot associate with water
Hydrophilic
Hydrophobic
Hydraulic
Hydrogen
Capable of associating with or absorbing water
Hydrophilic
Hydrophobic
Hydrologic
Hydraulic
The blood filtering process of the nephron
Glomerular filtration
Disposition
Complexion
Enzyme
The time a drug will stay in the stomach before it is emptied into the small intestine
Glomerular filtration
Gastric emptying time
Disposition
Agonist
The decrease in hepatic enzyme activity that results in reduced metabolism of drugs
First-pass metabolism
Hydrophilic
Gastric emptying time
Enzyme inhibition
A complex protein that catalyzes chemical reactions
Enzyme
Enzyme induction
Enzyme inhibition
Enzymes from fruit
The transfer of drugs and their metabolites from the liver to the bile in the gall bladder, then into
the intestine, and then back into circulation
Enzyme
Enterohepatic cycling
First-past metabolism
Glomerular filtration
The porcess of metabolism and excretion
Elimination
Disposition
Antagonists
Absorption
The time the drug concentration is above the MEC.
Elimination
Dosposition
Duration of action
Absorption
A term sometimes used to refer to all the ADME processes together.
Complexation
Disposition
Enzyme inhibition
Enzyme
When different molecules associate or attach to each other
Biopharmaceutics
Elimination
Complexation
Bio hazzard
The movement of drugs from an area of the lower concentration to an area of higher concentration;
requires cellular energy
Active transport
Absorption
Antagonist
Agonist
The movement of drug from the dosage formulation to the blood
Absorption
Active transport
Hydrate
First-pass metabolism
Drugs that activate receptors to accelerate or slow normal cellular function
Antagonist
Agonists
Disposition
Lipoidal
Drugs that bind with receptors but do not activate them
Agonists
Antagonist
Antiviral
Antibacteria
Fat like substance
Grease
Chicken
Emulsion
Lipoidal
The attachment of a drug molecule to a protein, effectively making the drug inactive
Metabolite
Metabolite
Protein binding
None of the above
The cellular material which interacts with the drug
Selective (action)
Receptor
Selective (action)
Onset of action
The movement of drugs from and area of higher concentration to lower concentration
Pharmaceutical alternative
Passive diffusion
Receptor
Site of action
The characteristic of a drug that makes it action specific to certain receptors
Selective (action)
Passive diffusion
Nephron
Nephrons
The location where an administered drug produces and effect
Systemic effect
Onset of action
Site of action
Selective (action)
The blood concentration needed for a drug to produce a response
Metabolite
Minimum effective concentration (MEC)
Minimum toxic concentration (MTC)
The time MEC is reachedc and the response occurs.
Onset of action
Passive diffusion
Systemic effect
Site of action
A drug's blood concentration range between its MEC and MTC.
Therapeutic equivalent
Therapeutic window
Receptor
Onset of action
The upper limit of the therapeutic window
Minimum toxic concentration (MTC)
Minimum effective concentration (MEC)
Therapeutic window
Therapeutic equivalent
Drug products that containing identical amounts of the same active ingredient in the same dosage
form
Pharmaceutical altnerative
Passive diffusion
Pharmaceutical equivalent
Pharmaceutical equivalent that produce the same effects in patients
Therapeutic equivalent
Therapeutic window
Minimum effective concentration (MEC)
Minimum toxic concentration (MTC)
Drug products that contain the same active ingredient but not necessarily in the same salt form,
amount, or dosage form
Pharmaceutical equivalents
Passive diffusion
Receptor
Pharmaceutical alternative
The place where a drug causes and effect to occur is called the
Site of action
Site of administration
Therapeutic window
Minmum toxic concentration (MTC)
Drug produces its effect at a/an _____ level
Tissue
Atomic
Molecular
Organ
Drug action can be caused by a
Physical action, such as a protective ointment
Chemical action, such as an antacid neutralizing acidity
Osmotic action, such as moving water out of tissues into blood
All of the above
An antagonist will
Not bind to a receptor
Accelerate a normal body process
Prevent other from binding to a receptor
Cause extended stimulation of receptor
In a blood concentration-time curve, the range between the minimum toxic concentration (MTC)
and the minimum effective concentration (MEC), is called the
Onset of action
Concentration at site of action
Duration of action
Therapeutic window
The time a drug's blood concentration is above the MTC is called the
Onset of action
Duration of action
Concentration at site of action
None of the above
When studying concentration and effect, the ____ is the time MEC is reached and the response
occurs
Therapeutic window
MTC
Onset of action
Duration of action
If the blood concentration-time profile reflects the amount of drug at the site of action, the
maximum therapeutic response would occur
At the onset of action
At the MEC
At the peak blood concentration
When elimination is the predominant process
The transfer of a drug out of a dosage form and into the blood is called
Absorption
Dissolution
Metabolism
Elimination
Blood concnetrations are the result of ______ simultaneously occurring processes, which together
are referred to as _____
Two, passive diffusion
Four, disposition
Three, elimination
Five, absorption
Unionized drugs are
Actively transported
Hydrophobic drugs
Passively diffused through membranes
Hydrophilic drugs
Which processes can influence the absorption of drugs given orally?
First-pass metabolism
Intestinal transit time
Gastric emptying
All of the above
Which formulation does not have an absorption step?
Intravenous sol.
Intramuscular emulsion
Topical cream
Vaginal suppository
When drug molecules are bound to plasma or tissue proteins they are
More potent
Metabolized
Inactive
Excreted
An enzyme in a complex _____ that catalyzes chemical reactions
Lipid
Mineral
Protein
Atom
When some drugs are chronically administered, the liver will decrease its enzyme activity. this is
called
Enzyme induction
Enzyme inhibition
Enzyme secretion
First pass metabolism
Enterohepatic recycling occurs when a
Drug is metabolized to a metabolite
Drug is secreted to the intestines along with the bile
Drug is secreted into the intestines along with the bile and reabsorbed back into the blood
circulation
All of the above
Elimination is
Absorption and metabolism
Metabolism and excretion
Distribution and excretion
Distribution and metabolism
Which set of circumstances will result in a drug undergoing urinary reabsorption?
Basic drug in high urine pH
Basic drug in low urine pH
Acidic drug in high urine pH
None of the above
The amount of drug excreted in the urine is the amount
Filtered + secreted + reabsorbed
Filtered + secreted - reabsorbed
Filtered - secreted + reabsorbed
Filtered - secreted - reabsorbed
The percentage or fraction of the administered dose of a drug that actually reaches the system
circulation and the rate at which this occurs is the drug's
Bioequivalence
Bioavailability
Biotransformation
Biopharmaceutics
To determine the bio availability of a drug product, it must be compared to another product
containing the same drug. If the second product is an intravenous solution, the bio availability is
termed
Relative
Bio equivalent
Redundant
Absolute
For elimination of a drug to be essentially complete, ___ times the half-life must elapse.
Two
Three
Five
Seven
Which of the following does NOT related with Biopharmaceutics?
Pharmaceutics including cience of drug formulation, Drug delivery or Physical pharmacy
Pharmacology - Pharmacokinetics/Pharmacodynamucs
Physiology with special emphasis on Cell-based transport
Pharmacy practice with special emphasis on clinical pharmacy
Biopharmaceutics considers:
Interrelationship of the physicochemical properties of the drug
Dose of a drug that produce a therapeutic effect.
Only the oral administration of drug and the rate and extent of drug absorption.
Advantages and disadvantages of various rout of drug administration on the rate and extent
of systemic drug absorption.
If plasma concentrations are plotted against time on linear X-Y graph paper, the curve is a/an
Exponential
Straight line
Bell shaped
Zigzag - graph
The rate-limiting step in the bioavailability of a lipid-soluble drug formulated as an immediate-
release compressed tablet is the rate of
Disintegration of the tablet and release of the drug
Dissolution of the drug
Transport of the drug molecules across the intestinal mucosal cells blood flow to the GIT.
Biotransformation of the drug by the liver prior to systemic absorption.
A line of best fit can be roughly determined using an
Eye level Method
Eyeball Method
Method of Residuals
Trapezoidal Method

Which one of these is a physicochemical property of Drug substance?

Drug solubility
Disintegration time
Age of patient
Dissolution time
Which one of these does not come under a physicochemical property of drugs?
Drug solubility
Disintegration time
Dissolution rate
Drug stability
In the sequence of events in the drug absorption from orally administered solid dosage, which one
comes at first?
Disintegration
Disaggregation
Dissolution
Absorption
Which one is the correct sequence for drug absorption through the oral route?
Absorption – Dissolution – Disintegration – Deaggregation
Disintegration – Dissolution – Deaggregation – Absorption
Disintegration – Deaggregation – Dissolution – Absorption
Disintegration – Deaggregation – Absorption – Dissolution
Patient-related factors of drug absorption do not deal with which one of these?
Age
Gastric Emptying time
Intestinal transit time
Pharmaceutic ingredients
The rate at which drug reaches the systemic circulation is determined by the slowest of the
various steps involved in the sequence. This is known as ____________
Disintegration time
Dissolution time
Rate limiting step
Gastric Emptying time

The process of absorption is governed by all of the followings EXCEPT:

The dissociation constant of the drug.
The dissociation constant of the fluid present at absorption site.
The lipid solubility of the unionized drug.
The pH at the absorption site.
The factors that may contribute to the deviations from pH-partition theory is (are),
Absorption of the ionized form of the drug.
Presence of an aqueous unstirred duffusion layer adjacent to the cell membrane.
Difference between luminal pH and pH at the surface of the cell membrane.
All of the choice.

Mathematical fundamentals,
Biostatistics Fundamentals, Rates
and order of processes.

To understand algebraically and graphically exponential and logarithms.

To understand and use linear (Cartesian) and semi-log graph paper for
the representation of data.

To review differential and integral calculus

To understand and use spreadsheets

To understand the theory, instrumentation and application of

spectrophotometric methods of analysis
Define various models representing rates and order of reactions and
calculate pharmacokinetic parameters (eg, zero- and first-order) from
experimental data based on these models.

Basic statistical methodology may be used in pharmacokinetic and

pharmacodynamics study design.

Mathematics (from Greek - máthēma:

'knowledge, study, learning') includes the
study of such topics as quantity (number
theory - Arithmetic), structure (algebra), space
(geometry), and change (Calculus). Through
the use of abstraction and logic, mathematics
developed from counting, calculation,
measurement, and the systematic study of the
shapes and motions of physical objects.

Greek mathematician Euclid (holding calipers), 3rd

century BC, as imagined by Raphael in this detail from
The School of Athens (1509–1511).

Kinetics is the branch of Mathematics that deals with

the effects of forces upon the motions of material
bodies or with changes in a system.

Pharmacokinetics is a mathematical subject.

Pharmacodynamics also uses the mathematical tools
to express drug action. It deals in quantitative
conclusions, such as a dose or a concentration of drug
in the blood.

Pharmacokinetics, Pharmacodynamics and

biopharmaceutics have a strong mathematical basis
in mathematical principles (algebra, calculus,
exponentials, logarithms, and unit analysis).

Most of the mathematics needed may be performed

with pencil, graph paper, and logical thought
processes.

Kinetics timeline

VARIABLES

A variable is something that changes over time.

A random variable is one whose observed values may be considered

as outcomes of an experiment and whose values cannot be
anticipated with certainty before the experiment is conducted.

An independent variable is the intervention or what is being

manipulated in a study (eg, the drug or dose of the drug being
evaluated). The number of independent variables determines the
category of statistical methods that are appropriate to use.

A dependent variable is the outcome of interest within a study. In

bioavailability and bioequivalence studies, examples include the
maximum concentration of the drug in the circulation. There may be
multiple dependent variables. For example, in a study determining
the half-life, clearance, and plasma protein binding of a new drug
following an oral dose, the independent variable is the oral dose of
the new drug. The dependent variables are the half-life, clearance,
and plasma protein binding of the drug because these variables
“depend upon” the oral dose given.

CONSTANTS AND PARAMETERS

A constant is time invariant.

There is, however, a special term used for a constant

that may, in fact, be a variable under a particular set of
circumstances. In particular for pharmacokinetics, a
parameter is a value that is constant for a given
individual receiving a particular drug. This value will
most likely vary for the same subject receiving a
different drug and may vary for different subjects
receiving the same drug. This value may also vary for a
given subject receiving a particular drug if it is
measured over a long time period (e.g. months) or if a
disease or drug interaction has occurred since the
value was last calculated.

Derived parameters are parameters that can be

estimated given the real or beta parameter
estimates.

When descriptive measures are calculated using

population data, those values are called
parameters. When we calculate descriptive
measures using sample data, the values are called
estimators or calculated parameters.

The primary pharmacokinetic disposition

parameter is clearance. volumes of distribution

Half-life is a secondary parameter.

TYPES OF DATA (NONPARAMETRIC VERSUS PARAMETRIC)

Discrete variables are also known as counting or

nonparametric variables: (Nominal and ordinal)

For nominal data, numbers are purely arbitrary or

without regard to any order or ranking of severity.
Nominal data may be either dichotomous or
categorical.

Dichotomous (aka binary) nominal data evaluate yes/no

questions. For example, patients lived or died, were
hospitalized, or were not hospitalized.

Examples of categorical nominal data would be things like

tablet color or blood type; there is no order or inherent
value for nominal, categorical data.

Ordinal data are also nonparametric and categorical,

but
unlike nominal data, ordinal data are scored on a
continuum, without a consistent level of magnitude of
difference between ranks. Examples of ordinal data
include a pain scale,(poor/ fair/good/very
good/excellent).

Continuous variables/measuring/parametric
variables. There is an order and consistent level of
magnitude of difference between data units.

Interval and ratio. Both interval and ratio scale

parametric data have a predetermined order to
their numbering and a consistent level of magnitude
of difference between the observed data units.

Variables and constants

There are obvious constants:

= 3.14159265
explicit numbers, such as 3,

e = 2.718282
18.5, (7/8)2

Time (t) is a variable.

Cp varies as a function of time. (There is one exception
where a combination of intravenous bolus and intravenous
infusion can result in constant Cp over time.)

The first order elimination rate constant (K) is a

constant, as the name implies.

An expression containing nothing but constants

yields a constant:

An expression containing a single variable yields a variable:

where a, b are constants; x, y are variables

A product of two variables will be a variable. The exception

is when the two variables are inversely proportional.

where a, b and c are constants and x, y and z are variables

A quotient of two variables will be a variable. The

exception is when the two variables are directly
proportional.

where a, b and c are constants and x, y and z are variables

Significant figures

There are two kinds of numbers: absolute numbers and denominate numbers.
An example of an absolute number would be seen in a problem in which you
are asked to calculate plasma drug level at a time two elimination half lives
after a dose is given. In this case the number is exactly 2.0000000000. . . to an
infinite number of decimal points.

However, when things are measured, such as doses or plasma drug levels,
there is some degree of uncertainty in the measurement and it is necessary to
indicate to what degree of precision the value of the number is known. This is
called a denominate number. Precision is indicated in these numbers by
reporting them to a certain number of significant figures. Significant figures
may be defined as the digits in a number showing how precisely we know the
value of the number. Significant figures are not to be confused with the
number of digits to the right of the decimal place. Some digits in a number
simply serve as placeholders to show how far away the rest of the digits are
from the decimal point.

For example, each of the following (Table bellow) numbers has three
significant figures. This can be more readily appreciated by expressing them in
scientific notation.
In performing pharmacokinetic calculations, we must take care to get the most
precise answer that can be supported by the data we have. Conversely, we do
not want to express our answer with greater precision than we are justified in
claiming. The rules of significant figures will help us with this task.

Number

Scientific
notation

Remark

102.

1.02 X 102

The zero between non-zero

integers is significant

10.0

1.00 X 101

If a trailing zero after a decimal

point is expressed, it is intended
to be significant

1.23

1.23 X 100

Non-zero integers are significant

0.123

1.23 X 10-1

Zero before the decimal point is

not significant

0.00123

1.23 X 10-3

Leading zeros after the decimal

point are merely placeholders,
and not significant
Occasionally, it is unclear how many significant figures a number
possesses. For example, the number 100 could be represented in
scientific notation by 1x102, 1.0x102 or 1.00x102. The only
unambiguous way to express this number is by the use of
scientific notation.

A calculator performs its calculations with a great degree of

precision, although it may not show a large number of significant
figures in its default (two decimal point) mode. The student is
likely to run into trouble when transferring an excessively
rounded off value from the calculator to paper. Based on the
precision of numbers encountered in pharmacokinetic
calculations, a good rule of thumb for pharmacokinetic
calculations is as follows:

Be careful to retain at least 3 significant figures throughout all

pharmacokinetic calculations and also to report numerical answers to
3 significant figures

Rounding off data or intermediate answers to fewer significant figures

can waste precision and cause the answer to be incorrect.

Typical units used in pharmacokinetics

Mathematical rules for units

Retain units throughout the whole calculation and

present them with the numerical answer.

Some quantities are unitless (e.g. fraction of drug

absorbed, F). Unitless numbers generally arise from
the fact that units of ratios cancel. For example, F is
the ratio: (AUC)oral/(AUC)IV.

Add or subtract only those numbers with the same

units, or which can be reduced to the same units. For
example:

1mg + 1mg = 2mg

1 h-1 + 2 h-1 = 3 h-1

1 h + 10 min = 60 min + 10 min = 70 min (inter convertible

units of time)

Exponentiate (raise to a power of e) unitless

numbers only. For example, for K = 1h-1 and t
= 2h,
(units cancel)

Multiply and divide units as for numbers. For

example:

Exponents

In the expression: N = bx or N = b^x (when b is

raised to the xth power)

N is the number, b is the base, [often 10 but

also e ( = 2.7183)], and x is the exponent

With common base, exponents can be added

or subtracted

e.g. ax * ay = a(x+y) to perform multiplication

or division.

Logarithms

The logarithm of a positive number N to a given base b is

the exponent (or the power) x to which the base must
be raised to equal the number N. Therefore, if

If N = bx then x = logb N

e.g. 100 = 102 thus log (100) = 2 base 10 assumed

100 is the antilog of 2.

These are called common Logarithms/logs.

Natural logs (ln) use the base e (=2.7183)

To convert from common to natural:-

2.303 x log N = ln N

e.g. ln (100) = 2.303 x log (100) = 2.303 x 2 = 4.606

A logarithm is an exponent.

A logarithm does not have units.

A logarithm is dimensionless and is considered

a real number.
The logarithm of 1 is zero.

The logarithm of a number less than 1 is a

negative number.

The logarithm of a number greater than 1 is a

positive number.

Special interest is the following relationship:

For many processes in nature, the rate of removal or

modification of a species is proportional to, and driven by,
the amount of that species present at a given time. This is
true for the kinetics of diffusion, chemical reactions,
radioactive decay and for the kinetics of the ADME
processes of pharmaceuticals. Systems of this type are
naturally described by exponential expressions.
Consequently, in order to evaluate many pharmacokinetic
expressions, it is necessary to have facility in the use of
operations involving exponential expressions and their
inverse expressions (logarithms).
Common logs are used with equilibrium equations and
buffer or pH calculations. Logarithms to base e are used in
pharmacokinetics.

GRAPHS

The construction of a curve or straight line by plotting

observed or experimental data on a graph is an
important method of visualizing relationships
between variables. By general custom, the values of
the independent variable (t, in pharmacokinetics it is
time) are placed on the horizontal line in a plane, or on
the abscissa (x axis), whereas the values of the
dependent variable (Cp, in pharmacokinetics it is drug
concentration) are placed on the vertical line in the
plane, or on the ordinate (y axis). The values are usually
arranged so that they increase linearly or
logarithmically from left to right and from bottom to
top.

Graph type

Rectangular coordinate
graph paper

Semilog coordinates graph

paper

Figure Linear Plot of Cp versus Time

Linear Plot of ln Cp versus Time

Semi-log Plot of Cp versus Time

How to draw a Cartesian graph

Give a Graph title.

Make the best use of the graph paper

(sensible range for the axes that makes the
best use of the available space,)

Use a sharp pencil

Plot your point (points are in right place)

clearly and add the line

Join the points, or use a line of best fit.

Clearly label the axes - don’t forget any units

Starting from the left (in fig bottom), we

see labels from 1 to 10, repeated three
times. Each segment labeled from 1 to 10 is
called a cycle. This sample has 3 cycles. The
labeling already printed on the paper is for
convenience only; the user must relabel the
axes to suit the data.

For example, suppose we want to plot data

values ranging from 2 units to 800 units on
this three cycle log scale. The first cycle is
labeled "as is" from 1 to 9. The second
cycle is relabeled 10, 20, 30, 40, 50, 60, 70,
80, and 90. The third cycle is relabeled 100,
200, etc. to 1000.

Each cycle covers a range of values spanning one

factor of 10. The next cycle covers a range 10
times larger, etc. The value zero does not appear
on a logarithmic scale, for log (0) = minus infinity.

The user has less freedom in labeling a log scale

than a linear one. The scales are directed, i.e.,
one-way, and cannot be labeled in the opposite
direction.

The underlying principle of the log scale is that

lengths along the scale are proportional to the
logarithms of the plotted values. The C and D
scales of slide rules are constructed the same
way.

The user must carefully examine the markings of the

scale to correctly interpret its subdivisions. Some
intervals have 10 subdivisions, some only five (every
second one of the ten being shown). Errors in the use
of log paper result from failure to notice these
differences in the way subdivisions are labeled.

Graph papers with one linear and one logarithmic

scale are called semi-logarithmic, log-linear, or
simply logarithmic. Graph papers with both scales
logarithmic are called log-log, full log, or dual
logarithmic.

As is evident from the 10 divisions of each cycle,

these logarithmic scales represent base-10
logarithms

Drawing a best-fit line through the Data

Drawing a line through the data doesn't mean through

just two data points but through all the data points. Be
especially careful about picking two adjacent data points.
Sometimes the first and last point can work but the last
point, the lowest concentration data point will probably
be inaccurate. The best approach is to put the line
through all the data. There should be points above and
below the line.

Begin by plotting all data.

Draw a shape that encloses all of the data, (try to make

it smooth and relatively even).

Draw a line that divides the area that encloses the data
in two even sized areas.

A line of best fit can be roughly determined

using an EYEBALL METHOD by drawing a
straight line on a scatter plot so that the number
of points above the line and below the line is
about equal (and the line passes through as
many points as possible).

The closer these correlation values are to 1 (or

to –1), the better a fit our regression equation is
to the data values. If the correlation value (being
the "r" value that our calculators spit out) is
between 0.8 and 1, or else between –1 and –0.8,
then the match is judged to be pretty good.

Slopes, rates and derivatives

Slope or gradient of a line is a number that describes

both the direction and the steepness of the line.

A rate is the ratio between two related quantities in

different units. In describing the units of a rate, the
word "per" is used to separate the units of the two
measurements used to calculate the rate (for example
a heart rate is expressed "beats per minute").

Derivatives is the rate of change of a function with

respect to a variable. Derivatives are fundamental to
the solution of problems in calculus and differential
equations.

Construction of pharmacokinetic sketches (profiles)

Method for creating profiles (sketches)

You will be asked to sketch A versus B (A as a

function of B). When presented in this form, the
convention is that A is the y-axis variable (the
dependent variable) and B is the x-axis variable
(the independent variable). For example:

Next, you will need to (find) and apply the

appropriate equation containing the y and x
variables you have been asked to sketch. For this
example, the equation is:

Note that we do not have to know the

pharmacokinetic interpretation of the symbols at this
point. All we need to know is that τ and

are variables and, for the purposes of constructing the

sketch, all the other symbols will be considered to be
constants.

Next, rearrange the equation to isolate the y

variable on the left side of the equal sign. For
example:

The equation is now in the form where y is a

function of x. This means that the value of the y
variable depends on the value of the x variable
and on some constants. (Note that even time
should be considered constant for the purpose of
the sketch if it is not the x variable for the sketch.)
Next, rewrite the equation grouping all the
individual constants together as a single constant
called CON. In this example:

Now determine which of the four basic sketch

types this equation represents. You may need to
do some more rearranging of the equation in
order to recognize which family it belongs to. Here

Introduction to Biopharmaceutics

Pharmacy

Definition

Branches of
Pharmacy

Evolution of
Pharmacy

Current and future

trend in pharmacy

Pharmaceutics

Definition and scope

of Pharmaceutics

Pharmacology

Definition of
Pharmacology

Branches of
Pharmacology
Biopharmaceutics

Definition of
Biopharmaceutics

Drug Product

Invention (NDA, ANDA)

Brand drug product

Generic drug product

Introduction to Biopharmaceutics (cont’d)

3. Pharmacokinetic Introduction

Pharmacokinetics

Definition of Pharmacokinetics

Pharmacokinetic Models

Compartment Models

Mammillary Model

Catenary Model

Physiologic Pharmacokinetic Model (Flow Model)

Clinical Pharmacokinetics

Pharmacodynamics

Toxicokinetics and clinical Toxicology

Measurement of drug concentrations

Sampling of Biologic Specimens, Drug

Concentrations in Blood, Plasma, or
Serum, Plasma Level–Time Curve, Drug
Concentrations in Tissues, Drug
Concentrations in Urine and Feces, Drug
Concentrations in Saliva, Forensic Drug
Measurements, Significance of
Measuring Plasma Drug Concentrations,
Introduction to Biopharmaceutics (cont’d)

4. Background Material

Mathematical fundamentals

Exponents

Logarithms

Semi-log graph paper

Calculus

Differential Calculus

Integral Calculus

Spreadsheet Calculations

Biostatistics Fundamentals

Variables

types of data

Distributions

controlled vs. noncontrolled studies etc.

Spectrophotometric Analysis

Rates and orders of reactions

Pharmacy

The art or practice of preparing and preserving drugs, and

of compounding and dispensing medicines according to
prescriptions of physicians; the occupation of an
apothecary or a pharmaceutical chemist.

A place where medicines are compounded; a drug store;

an apothecary's shop.

The main purpose of this narrow field of education is to

develop an understanding of the properties of drugs and
medical products and their manufacture, control and use
in the community and hospitals.

Biopharmaceutics

A study of the factors influencing the bioavailability

and disposition of drugs (how the physicochemical
properties of drugs, dosage forms and routes of
administeration affect the rate and extent of the drug
absorption), and the application of this information
to optimise the therapeutic usefulness of drugs in
clinical practice. Particular emphasis is placed on the
clinical role of the Pharmacist in improving the use of
drugs through the practical application of
pharmacokinetics.

Biopharmaceutics examines the interrelationship

of the physical/ chemical properties of the drug,
the dosage form (drug product) in which the
drug is given, and the route of administration on
the rate and extent of systemic drug absorption.
The importance of the drug substance and the
drug formulation on absorption, and in vivo
distribution of the drug to the site of action, is
described as a sequence of events that precede
elicitation of a drug’s therapeutic effect.

Biopharmaceutics: Integration of Physical

/Chemical and Biological/ Pharmacokinetic
Principles and Impact on Clinical Efficacy

Biopharmaceutics has evolved into a broad-based

discipline that encompasses fundamental principles from
basic scientific and related disciplines, including chemistry,
physiology, physics, statistics, engineering, mathematics,
microbiology, enzymology, and cell biology. The
biopharmaceutical scientist, therefore, must have
sufficient understanding of all of these scientific fields in
order to be most effective in a drug development role. A
scientist educated in the field of biopharmaceutics or
biopharmaceutical sciences could have expertise in a
number of interrelated specialty disciplines including
formulation, pharmacokinetics (PK), cell-based transport,
drug delivery, or physical pharmacy.

Biopharmaceutics considers

interrelationship of the physicochemical

properties of the drug
dosage form in which the drug is given

route of administration on the rate and

extent of systemic drug absorption.

Biopharmaceutics involves factors that

influence the

(1) protection of the activity of the drug within

the drug product,

(2) the release of the drug from a drug product

(3) the rate of dissolution of the drug at the

absorption site

(4) the systemic absorption of the drug.

Scheme demonstrating the dynamic relationships

among the drug, the product, and pharmacologic
effect.

Studies in biopharmaceutics use

in vitro “in the glass” in Latin, and refers to just that—when live
cells are removed from the organism and tested in an artificial,
controlled environment. An example would be growing cancer
cells in a dish outside of the body to study them and possible
treatments.

In vivo (Latin for “within the living”) is the study of the biological
effects of a drug in a complex living organism and is used to
observe the complex physiological effects of a drug. Examples can
include studies in animal models or human clinical trials.

In situ is a Latin phrase that translates literally to "on site" or "in

position." It can mean "locally", "on site", "on the premises", or "in
place" to describe where an event takes place and is used in many
different contexts.

in silico experiment is one performed on computer or via

computer simulation. The phrase is pseudo-Latin for "in silicon",
referring to silicon in computer chips.

Physical Pharmacy: Physical–Chemical Principles

Solubility
A thermodynamic parameter impacts its usefulness as a
medicinal agent and also influences how a compound is
formulated, administered, and absorbed.

Hydrophilicity/Lipophilicity

The relative lipophilicity is important with respect to

biopharmaceutics since it affects partitioning into
biological membranes and therefore influences
permeability through membranes as well as binding and
distribution into tissues in vivo

Salt Forms and Polymorphs

The impact of pH and salt form on solubility, and how this

phenomenon can be utilized to manipulate the solubility
behavior of a drug compound

Stability

Important in order to avoid generation of undesirable impurities, which

could have pharmacologic activity and/or toxicologic implications, in the
drug substance or drug product

Particle and Powder Properties

Important from the perspective of a manufacturing process while

others could potentially impact drug product dissolution rate without
changing equilibrium solubility.

Ionization and pKa

Influences all of the physical–chemical properties discussed above. The

presence of an ionizable group leads to pH solubility effects, which can
be used to manipulate the physical properties and biological behavior of
a drug. For an ionizable compound, the aqueous solubility of the ionized
species is typically higher than the unionized due to the greater polarity
afforded by the presence of the ionized functional group. The ionizable
functional group and the magnitude of the pKa determine whether a
compound is ionized across the physiological pH range, or if conversion
between ionized/nonionized species occurs in the GI tract, and if so,
which region. The pKa also affects the available choices of counterions
for potential salt forms that are suitable from a physical perspective.

Formulation Principles

The goal is to manipulate the properties and environment

of the API to optimize its delivery to the target tissue by a
specific route of administration and to do so in a manner
compatible with large-scale product manufacture.
Excipients are added to solubilize, stabilize, modify
dissolution rate, improve ease of administration, enable
manufacturing, control release rate, or inhibit
precipitation. The formulation is key to a compound’s
biopharmaceutical profile since the composition, dosage
form type, manufacturing process, and delivery route are
intimately linked to pharmacokinetic results. A PK
assessment cannot be complete without inclusion of the
relevant formulation parameters to establish the
appropriate context.

PHYSIOLOGICAL
/BIOLOGICAL
PRINCIPLES

Pharmacokinetics

What the body does to the drug

Pharmacodynamics

What the drug does to the body

PHARMACOKINETICS

Pharmacokinetics involves

Kinetics (temporal and spatial distribution of a substance in a system) of drug

absorption, distribution, and elimination (ie, excretion and metabolism)

The study of pharmacokinetics involves

Experimental - development of biological sampling techniques, analytical

methods for the measurement of drugs and metabolites, and procedures that
facilitate data collection and manipulation

Theoretical approaches –development of pharmacokinetic models that

predict drug disposition after drug administration

Statistical methods

-used for pharmacokinetic parameter estimation and data interpretation

-applied to pharmacokinetic models to determine data error and structural

model deviations. Mathematics and computer techniques form the
theoretical basis of many pharmacokinetic methods. Classical
pharmacokinetics is a study of theoretical models focusing mostly on model
development and parameterization.

PHARMACOKINETICS (continued)

Pharmacokinetics is the study of drug and/or

metabolite kinetics in the body. It deals with a
mathematical description of the rates of drug
movement into, within and exit from the body. It
also includes the study of drug metabolism or
biotransformation rates. The body is a very complex
system and a drug undergoes many steps as it is
being absorbed, distributed through the body,
metabolized or excreted (ADME).

Fate of Drug

Pharmacokinetics

What the body does to the drug

Drug at
Absorption
Site

Drug in Body

Excreted Drug

Metabolites

Absorption

Excretion

Metabolism

Distribution

Pharmacokinetic Terms

AUC
Area Under the Curve or

Area under the concentration-time curve

Cmax
Maximum (peak) drug concentration

Tmax
Time of peak drug concentration

t1/2
Half-life; the amount of time required for the amount (or concentration)
of a drug to decrease by one-half

CL
Systemic clearance; measure of the body’s ability to eliminate drug
(volume per unit time)

V
Volume of distribution; relates the amount of drug in the body to the
concentration of drug in the blood

Key Pharmacokinetic Parameters Illustrated

Cmax: maximum observed

concentration

Tmax: time of Cmax

Elimination half-life
(t1/2 ): time to eliminate 50% of
the drug from the body

AUC: area under the curve;

gauge of systemic
exposure/availability

t1/2

0.
1

10

0
6

12

18

24

30

36

Time (hrs)

Cmax

Tmax

Drug
Concentration

PHARMACODYNAMICS

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. The
interaction of a drug molecule with a receptor causes
the initiation of a sequence of molecular events
resulting in a pharmacologic or toxic response.
Pharmacokinetic pharmacodynamic models are
constructed to relate plasma drug level to drug
concentration in the site of action and establish the
intensity and time course of the drug

Pharmacodynamics

What the drug does to the body

Drug at
Absorption
Site

Drug in Body
Excreted Drug

Metabolites

Absorption

Excretion

Metabolism

Distribution

Drug at
Effect Site

Response

Pharmacodynamic Terms

Emax
Maximum effect

ED50
Dose which produces 50% (half) of the maximum effect

EC50
Concentration which produces 50% (half) of the
maximum effect

Key Pharmacodynamic Parameters Illustrated

Emax: maximum observed

effect

ED50: Dose which produces

50% (half) of the maximum
effect

EC50: Concentration which

produces 50% (half) of the
maximum effect

Emax
ED50 or EC50

Plasma Level-Time Curve

Generated by measuring the drug concentration

in plasma samples taken at various time intervals
after a drug product is administered

The concentration of drug in each plasma sample

is plotted against the corresponding time at which
the plasma sample was removed.

MEC – minimum effective concentration

MTC – minimum toxic concentration

Onset time

Duration of drug action

Peak plasma level

Area Under the Curve, or AUC

Drug Product Performance Parameters:

1- Minimum effective concentration (MEC): The minimum

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

2- Minimum toxic concentration (MTC): The drug concentration

needed to just produce a toxic effect.

3- Onset time: The time required for the drug to reach the MEC.

4- Duration of action: The difference between the onset time and

the time for the drug to decline back to the MEC.

5- The time of peak plasma level: The time of maximum

drug concentration in the plasma and is proportional
to the rate of drug absorption.

6- The peak plasma level: The maximum drug

concentration, usually related to the dose and the
rate constants for absorption and elimination of the
drug.
7- Area under the curve: It is related to the amount of
drug absorbed systemically.

Drug in dosage form

Relea
se

Drug particles in body fluids

Dissolution

Drug in solution

Degradation

Absorption

Liver

Excretion

GI

Central Compartment

Free ⮀ Bound

Distribution

Peripheral

Tissues

Pharmacologic effect

Pharmacodynamics

Biopharmaceutics

Pharmacokinetics

BASIC PHARMACOKINETICS

Quantitative study of various kinetic processes

of drug disposition in the body.
Drugs are in a dynamic State within the body.

The biological nature of drug distribution and

disposition is complex

Drug events often happen simultaneously.

Basic pharmacokinetics requires –

A thorough knowledge of anatomy and

physiology

An understanding of the concepts and

limitations of mathematical models.

CLINICAL PHARMACOKINETICS

Relating to the observation and

treatment of actual patients rather
than theoretical or laboratory studies.

Clinical pharmacokinetics is the

discipline that describes the
absorption, distribution, metabolism,
and elimination of drugs in patients
requiring drug therapy.

Toxicology

the study of the adverse effects of chemical, physical, or

biological agents on people, animals, and the
environment. It involves observing and reporting
symptoms, mechanisms, detection and treatments of
toxic substances, in particular relation to the poisoning
of humans.

Toxicology is an interdisciplinary science, integrating

information from biology and virtually all of its
subspecialties (e.g., genetics, endocrinology and
molecular biology) as well as math, physics and
chemistry and its subspecialties (e.g. analytical, organic,
and clinical chemistry).

Toxicokinetics

Toxicokinetics refers to the study of absorption, distribution,

metabolism/biotransformation, and excretion (ADME) of
toxicants/xenobiotics in relation to time. The basic kinetic
concepts for the absorption, distribution, metabolism, and
excretion of chemicals in the body system initially came
from the study of drug actions or pharmacology; therefore,
this area of study is traditionally referred to
as pharmacokinetics. Toxicokinetics represents the
extension of kinetic principles to the study of toxicology and
encompasses applications ranging from the study of adverse
drug effects to investigations on how disposition kinetics of
exogenous chemicals derived from either natural or
environmental sources (generally referred to as xenobiotics)
govern their deleterious effects on organisms, including
humans.

Clinical Toxicology

the discipline within toxicology concerned

with the toxic effect of agents whose intent is
to treat, ameliorate, modify, or prevent
disease states, or the effect of drugs which, at
one time, were intended to be used as such.
But he expands it to include agents used with
non-therapeutic intent—for example, alcohol
and drugs of misuse and chemical byproducts
of industrial development.

Clinically, sound medical judgment

and observation are most
important. Therapeutic decisions
should not be based solely on
plasma drug concentrations.