General Pharmacology Lecture Slides on Bioavailability and Bioequivalence by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College
2. Basics
• For a drug to show its action, following steps
are necessary:
1. Absorption
2. Enter the systemic circulation (blood)
3. Reach the site of action
Orally given drugs: Steps 1,2,3
Injectable drugs: Steps 2,3
Topical drugs: Step 3
4. Let us suppose 50 ng/ml is the MEC.
What is the lag time for onset of action?
What is the duration of action for the drug?
5. Urinary Drug Excretion Data
Indirect method for assessing
Bioavailability
Collection of urine samples
and determination of total
quantity of drug excreted over
time
Urinary excretion of
unchanged drug is directly
proportional to plasma
concentration
6. Bioavailability
Bioavailability refers to the rate and extent of absorption
of a drug from a dosage form as determined by its
concentration-time curve in blood or by its excretion in
urine.
It is a measure of a fraction (F) of administered drug
that reaches the systemic circulation in a chemically
unchanged form.
In instances where local action is required- pain killer
sprays, the drug is not intended to be absorbed into the
bloodstream, so bioavailability may be assessed by
measuring the drug that gets to the site of action.
7. Bioavailability
• Bioavailability refers to the rate and extent of
drug that reaches the systemic circulation or
to the site of action in an unchanged form.
• Types
– Relative Bioavailability (Compared with standard drug)
– Absolute Bioavailability (Compared with IV route)
8. Relative Bioavailability
Relative (apparent) availability is the availability of the
drug from a drug product as compared to a recognized
standard.
The relative availability of two drug products given at
the same dosage level and by the same route of
administration can be obtained using the following
equation:
Relative bioavailability studies are needed to compare
the performance of the new with the original
formulation.
9. Absolute Bioavailability
The absolute availability of drug is the systemic
availability of a drug after extravascular
administration (eg, oral, rectal, transdermal,
subcutaneous) compared to IV dosing.
The absolute availability of a drug is generally
measured by comparing the respective AUCs after
extravascular and IV administration.
10. Bioavailability
Bioavailability of a drug injected i.v is 100%, but is frequently
low after oral injection because:
◦ The drug may be incompletely absorbed
◦ The absorbed drug may undergo first pass metabolism
Methods of assessing bioavailability
Plasma level data
Cmax The max concentration that can be attained
Tmax The time required to reach the Cmax
AUC Area under curve estimates extent of bioavailability
Urinary excretion data
Acute pharmacologic response
Heart rate, pupil size
11.
12. Plasma drug concentration-time
• Plasma drug concentration-time profile is used for the calculation of
various pharmacokinetics parameters such as
– Area under curve (AUC),
– Drug absorption constant (Ka ),
– Drug elimination constant (K),
– Volume of distribution (V d ) and
– others.
Area Under Curve
• AUC, an important pharmacokinetic parameter, provides basic
information regarding drug transit time in body because it is proportional
to the drug absorbed.
13. Area Under Curve
Statistically, there are many approaches such as:
– Rectangular rule,
– Trapezium rule, and
– Simpson’s rule
However, mostly the calculation of AUC is usually performed by
the trapezoidal rule.
Trapezoidal Rule: Will be dealt in practical
14. Bio-Equivalents
Relationship in terms of bioavailability, therapeutic
response, or a set of established standards of one drug product
to another.
Types:
I . Chemical Equivalents
It indicates that two or more drug products that contain the same chemical
substance as an active ingredient in the same amount.
II. Generic Equivalents
It indicates that two or more drug products with the same
generic formula but different brand name.
15. III. Pharmaceutic Equivalents
It indicates the two or more drug products containing
same active ingredient that are identical in strength,
quality, purity, content uniformity & disintegration ,
dissolution characteristics; they may however vary in
containing different excipients.
IV. Therapeutic Equivalents
It indicates two or more drug products containing the
same therapeutically active ingredients, elicit identical
pharmacological effects & can control the disease to
the same extent.
16. Bioequivalence
• Chemically equivalent (same amount of
the same active ingredient) and
pharmaceutically equivalent products (same
dosage form; e.g. conventional tablet), that
exhibit the same rate and extent of drug
absorption, are known to be bioequivalent.
• The bioequivalent products are considered to
be therapeutic equivalents.