Thi-Qar University

Chapter
College of Pharmacy
One
Biopharmaceutics

Introduction
Drugs, whether obtained from plant, animal or mineral sources or synthesized chemically,
are rarely administered in their pure chemical form. Often, they are combined with a
number of inert substances (excipients/adjuvants) and transformed into a convenient
dosage form that can be administered by a suitable route.
First, the drug in its dosage form is taken by the patient by an oral, intravenous,
subcutaneous, transdermal, etc, route of administration.
Next, the drug is released from the dosage form in a predictable and characterizable
manner.
Then, some fraction of the drug is absorbed from the site of administration into either the
surrounding tissue for local action or into the body (as with oral dosage forms), or both.
Finally, the drug reaches the site of action. A pharmacodynamic response results when the
drug concentration at the site of action reaches or exceeds the minimum effective
concentration (MEC).

Thus, biopharmaceutics involves factors that influence:

(1) The design of the drug product,
(2) Stability of the drug within the drug product,
(3) The manufacture of the drug product,
(4) The release of the drug from the drug product,
(5) The rate of dissolution/ release of the drug at the absorption site, and
(6) Delivery of drug to the site of action, which may involve targeting the drug to a localized
area (eg, colon for Crohn disease) for action or for systemic absorption of the drug.

The study of biopharmaceutics is based on fundamental scientific principles and

experimental methodology.
Studies in biopharmaceutics use both in vitro and in vivo methods:
In vitro methods are procedures employing test apparatus and equipment without involving
laboratory animals or humans.
In vivo methods are more complex studies involving human subjects or laboratory animals.

Pharmacokinetics is the science of the kinetics of drug absorption, distribution, and

metabolism and excretion (ADME).
The process of movement of drug from its site of administration to the systemic circulation
is called as absorption. The concentration of drug in plasma and hence the onset of action,
and the intensity and duration of response depend upon the bioavailability of drug from its
dosage form. Bioavailability is defined as the rate and extent (amount) of drug absorption.
Any alteration in the drug’s bioavailability is reflected in its pharmacological effects. Other
processes that play a role in the therapeutic activity of a drug are distribution and
elimination. Together, they are known as drug disposition. The movement of drug
between one compartment and the other (generally blood and the extravascular tissues) is
referred to as drug distribution. Since the site of action is usually located in the
extravascular tissues, the onset, intensity and sometimes duration of action depend upon
the distribution behavior of the drug.
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Figure (1): Schematic illustration of pharmacokinetic processes.

Pharmacodynamics 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. A typical example of pharmacodynamics is how a drug interacts
quantitatively with a drug receptor to produce a response (effect). Receptors are the
molecules that interact with specific drugs to produce a pharmacological effect in the body.
The pharmacodynamic effect, sometimes referred to as the pharmacologic effect, can be
therapeutic and/or cause toxicity.

MEASUREMENT OF DRUG CONCENTRATIONS

Because drug concentrations are an important element in determining individual or
population pharmacokinetics, drug concentrations are measured in biologic samples, such
as milk, saliva, plasma, and urine.
In general, chromatographic and mass spectrometric methods are most frequently
employed for drug concentration measurement, because chromatography separates the drug
from other related materials that may cause assay interference and mass spectrometry
allows detection of molecules or molecule fragments based on their mass-to-charge ratio.

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Drug Concentrations in Blood, Plasma, or Serum

Measurement of drug and metabolite concentrations (levels) in the blood, serum, or plasma
is the most direct approach to assessing the pharmacokinetics of the drug in the body.
Blood
Component
How Obtained Components
Whole blood is generally obtained by venous Whole blood contains all the
Whole Blood puncture and contains an anticoagulant such as cellular and protein elements of
heparin or EDTA. blood.
Serum is the liquid obtained from whole blood Serum does not contain the
after the blood is allowed to clot and the clot is cellular elements, fibrinogen, or
removed. the other clotting factors from the
Serum
blood.

Plasma is the liquid supernatant obtained after Plasma is the noncellular liquid
centrifugation of non-clotted whole blood that fraction of whole blood and
Plasma
contains an anticoagulant. contains all the proteins
including albumin.

Plasma Drug Concentration-Time Profile

A direct relationship exists between the concentration of drug at the biophase (site of
action) and the concentration of drug in plasma.
Two categories of parameters can be evaluated from a plasma concentration time profile:
Pharmacokinetic parameters, and Pharmacodynamic parameters.
A typical plasma drug concentration-time curve obtained after a single oral dose of a drug
and showing various pharmacokinetic and pharmacodynamic parameters is depicted in the
figure below. Such a profile can be obtained by measuring the concentration of drug in
plasma samples taken at various intervals of time after administration of a dosage form and
plotting the concentration of drug in plasma (Y-axis) versus the corresponding time at
which the plasma sample was collected (X-axis).

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Figure (2): A typical plasma concentration-time profile showing pharmacokinetic and

pharmacodynamics parameters, obtained after oral administration of single dose of a drug.

Figure (4): A typical plasma concentration-time profile showing pharmacokinetic and

pharmacodynamics parameters, obtained after IV administration of single dose of a drug.

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Pharmacokinetic Parameters
The three important pharmacokinetic parameters that describe the plasma level-time curve
and useful in assessing the bioavailability of a drug from its formulation are:
1. Peak Plasma Concentration (Cmax): The point of maximum concentration of drug
in plasma is called as the peak and the concentration of drug at peak is known as peak
plasma concentration. It is also called as peak height concentration and maximum drug
concentration. Cmax is expressed in mcg/ml.
The peak plasma level depends upon:
1. The administered dose.
2. Rate of absorption, and Rate of elimination.
The peak represents the point of time when absorption rate equals elimination rate of drug.
The portion of curve to the left of peak represents absorption phase i.e. when the rate of
absorption is greater than the rate of elimination. The section of curve to the right of peak
generally represents elimination phase i.e. when the rate of elimination exceeds rate of
absorption. Peak concentration is often related to the intensity of pharmacological response
and should ideally be above minimum effective concentration (MEC) but less than the
maximum safe concentration (MSC).
2. Time of Peak Concentration (tmax): The time for drug to reach peak concentration
in plasma (after extravascular administration) is called as the time of peak concentration.
It is expressed in hours and is useful in estimating the rate of absorption. Onset time and
onset of action are dependent upon tmax. This parameter is of particular importance in
assessing the efficacy of drugs used to treat acute conditions like pain and insomnia which
can be treated by a single dose.

3. Area Under the Curve (AUC): It represents the total integrated area under the plasma
level-time profile and expresses the total amount of drug that comes into the systemic
circulation after its administration. AUC is expressed in mcg/ml X hours. It is the most
important parameter in evaluating the bioavailability of a drug from its dosage form as it
represents the extent of absorption. AUC is also important for drugs that are administered
repetitively for the treatment of chronic conditions like asthma or epilepsy.

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Pharmacodynamic Parameters
The various pharmacodynamic parameters are:
1. Minimum Effective Concentration (MEC): It is defined as the minimum concentration
of drug in plasma required to produce the therapeutic effect. It reflects the minimum
concentration of drug at the receptor site to elicit the desired pharmacological response.
The concentration of drug below MEC is said to be in the sub-therapeutic level. In case of
antibiotics, the term minimum inhibitory concentration (MIC) is used. It describes the
minimum concentration of antibiotic in plasma required to kill or inhibit the growth of
microorganisms.

2. Maximum Safe Concentration (MSC): Also called as minimum toxic concentration

(MTC), it is the concentration of drug in plasma above which adverse or unwanted effects
are precipitated. Concentration of drug above MSC is said to be in the toxic level.

3. Onset of Action: The beginning of pharmacological response is called as onset of

action. It occurs when the plasma drug concentration just exceeds the required MEC.

4. Onset Time: It is the time required for the drug to start producing pharmacological
response. It corresponds to the time for the plasma concentration to reach MEC after
administration of drug.

5. Duration of Action: The time period for which the plasma concentration of drug
remains above the MEC level is called as duration of drug action. It is also defined as the
difference between onset time and time for the drug to decline back to MEC.

6. Intensity of Action: It is the maximum pharmacological response produced by the peak

plasma concentration of drug. It is also called as peak response.

7. Therapeutic Range: The drug concentration between MEC and MSC represents the
therapeutic range. It is also known as therapeutic window.

8. Therapeutic Index: The ratio of MSC to MEC is called as therapeutic index. It is also
defined as the ratio of dose required to produce toxic or lethal effects to dose required to
produce therapeutic effect.

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Figure (5): Pharmacokinetics (PK), pharmacodynamics (PD) and (PK/PD) models.

❖ Drugs that have to enter the systemic circulation to exert their effect can be
administered by three major routes:
1. The Enteral Route: includes peroral i.e. gastrointestinal, sublingual/buccal and
rectal routes. The GI route is the most common for administration of majority of
drugs.
2. The Parenteral Route: includes all routes of administration through or under one
or more layers of skin. While no absorption is required when the drug is
administered i.v., it is necessary for extravascular parenteral routes like the
subcutaneous and the intramuscular routes.
3. The Topical Route: includes skin, eyes or other specific membranes. The
intranasal, inhalation, intravaginal and transdermal routes may be considered enteral
or topical according to different definitions.