Bioavailability

And
Bioequivalence
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LECTURES BY- MAS
 BIOAVAILABILITY
 Bioavailability may also be defined as the rate and
extent to which the active drug is absorbed from a
dosage form and becomes available in the systemic
circulation and at site of action. or
 Bioavailability is a measurement of the extent of a
therapeutically active medicine that reaches the
systemic circulation and is therefore available at the
site of action..
 Bioavailability is concerned with how quickly and
how much of drug appears in circulation after a
specific dose is administered.
 It typically Represents “safe & effective dose" of
drug.
Purposes of Bioavailability
 Bioavailability studies are performed for
both therapeutic ingredients not yet
approved for marketing and approved active
drugs
For new drugs
 Rate and extent of systemic absorption
 Rates of excretion and metabolism
 Elimination half-life
To establish dosage regimens
 Dose, frequency of administration(how
many times), treatment duration (DFT)
To determine influence of
 Excipients
 Manufacturing procedures
 Patient related factors on biological
performance of new drug formulation
For Approved Drugs
 To develop new DF or to improve on
existing DF
 For its labeled indications of use
 Drug product must meet all applicable
standards of identity, strength, quality, and
purity.
 Bioavailability studies are required to ensure
safety and efficacy.
Types of Bioavailability
Absolute Bioavailability
 Absolute bioavailability is the actual percentage of
the administered dose (from 0 to 100%), which
reaches the general circulation. Estimation involves
comparing drug exposure following extravascular
(e.v.) administration of the tested dosage form with
that of an intravenous administration (i.v.), assumed
to be 100% available
 The route of extravascular administration can be
inhaled, intramuscular, oral, rectal, subcutaneous,
sublingual, topical, transdermal, etc.
 Absolute bioavailability compares drug absorption
between two routes: extravascular (like oral) and
intravenous (IV).It is calculated using the Area Under the
Curve (AUC), which measures the drug concentration over
time.
Relative Bioavailability
 Relative bioavailability involves
comparison of two formulations (or two
routes of administration of the same
formulation) without reference to an i.v.
administration. It should be emphasized
that interpretation of a relative
bioavailability trial can be of limited value
if the absolute bioavailability of the
reference formulation is not known.
Parameters of bioavailability
 Bioavailability parameters are measures used to assess the
extent and rate at which a drug becomes available to the body
after administration. The main bioavailability parameters are:
 1. Cmax (Maximum Plasma Concentration): The highest
concentration of the drug in the blood after administration.
 2. Tmax (Time to Reach Cmax): The time it takes to reach
the maximum plasma concentration.
3. AUC (Area Under the Curve): The
total amount of drug in the blood over a
specific time period.
4. Elimination Rate Constant: The rate
at which the drug is eliminated from the
body.
5. t1/2 (Half-Life): The time it takes for
the concentration of the drug to
decrease by half.
Significance of Bioavailability
 The significance of bioavailability lies in the following:
 1. Efficacy: Bioavailability determines the amount of
drug available to produce a therapeutic effect. Higher
bioavailability typically leads to better efficacy.
 2. Dosage: Knowing the bioavailability helps determine
the optimal dose to achieve the desired therapeutic effect.
Enhanced BA may increase the risk of overdose,
especially when adjustments are not made.
 3. Safety: higher bioavailability may
increase the risk of certain side effects.
i.e, increased peak plasma concentration
may lead to toxicity.
 Bioavailability also affects the risk of
adverse effects, as higher bioavailability
may increase the likelihood of dose-
related toxicities.
 4.Formulation Development: Bioavailability
guides the development of drug formulations,
such as tablets, capsules, or injectables, to
optimize drug delivery.
 5. Route of Administration: Bioavailability
differs between routes of administration (e.g.,
oral, IV, topical), impacting drug design and
administration.
FACTORS AFFECTING BIOAVAILABILITY
There are three major absorption factors,
1. The dose of drug administered, i.e. the blood level
will rise and fall in Proportion to the dose
administered.
2)The same as the first but brought about by a different
process of drug absorbed from a given dosage form. The
effect of only one half of the drug absorbed from a dosage
form is equivalent to lowering the dose.
3)The rate of absorption of the drug, if absorption from the
dosage form is more rapid than the rate of absorption then
toxic level can be exceeded. If absorption from the dosage
form is sufficiently slow minimum effective level cannot
be attained.
THE OTHER FACTORS ARE AS FOLLOWS
PHYSIOLOGICAL FACTORS
•Gastrointestinal fluids (pH, bile salts)
•Motility(gastric emptying, presence of food, rest and
exercise)
•Absorption surface(physiological integrity area).

PHARMACOLOGICAL FACTOR
•Variation in drug content
•Storage (drug and excipient stability)
•State of drug (particle size)
Bioequivalence
• Bioequivalence is the biochemical
similarity of two (or more) drugs
that share the same active
ingredient(s) and desired
outcome(s) for patients.
• If two medicines are
bioequivalent there is no clinically
significant difference in their
bioavailability.
Bioequivalence
 Bioequivalence is defined as the absence of a
significant difference in the rate and extent of
absorption into the systemic circulation, of two
pharmaceutically equivalent medicines, when
administered in the same dose under similar
conditions.
 Therapeutic effect (in terms of efficacy and safety)
of bioequivalent medicines is considered to be
essentially the same.
 A bioequivalence study is a specialized type of
relative bioavailability study
• According to FDA guidelines for bioequivalence, a
generic copy of a drug must contain identical
amounts of the active ingredient in the same dose
formulation and route of administration. Some
inactive ingredients (excipients) are allowed to differ
but must occur in a similar ratio to the active
ingredient as that observed in the innovator drug.
• It is accepted that if plasma concentrations of the
active ingredient of the generic and innovator
medicines are the same, then their concentration at
the site of action and therefore their safety and
effectiveness will be the same.
•Studies have demonstrated that actual
differences between observed mean
plasma concentrations of generic and
innovator medicines were no greater
than 5%. In order to determine that
two medicines are bioequivalent there
must be no more than a 20%
difference between the AUC and
Cmax.
 Bioequivalence studies are drug
product performance tests that
compare the bioavailability of the same
active pharmaceutical ingredient from
one drug product (test) to a second
drug product (reference).
 The report format for
bioequivalence studies
1. Study Protocol: A detailed description of the
study design and objectives.
2. Study Report:
 Introduction
 Methods
 Results
 Discussion
 Conclusion
3. Bioequivalence Analysis:
Pharmacokinetic parameters (e.g.,
AUC, Cmax, Tmax)
Statistical analysis (e.g., ANOVA).
Bioequivalence conclusion (e.g.,
failed, passed)
Important terms
 Equivalence: Relationship in terms of
bioavailability, therapeutic response, or a set of
established standards of one drug product to
another.
 Therapeutic equivalents: Drug products are
considered to be therapeutic equivalents only if
they are pharmaceutical equivalents and if they
can be expected to have the same clinical effect
and safety profile when administered to
patients under the conditions specified in the
labeling.
 Therapeutic substitution: The process
of dispensing a therapeutic alternative
in place of the prescribed drug product.
 For example, amoxicillin is dispensed
instead of ampicillin or ibuprofen is
dispensed instead of naproxen.
 Pharmaceutical alternatives: Drug products that
Contain the same therapeutic moiety but as
different salts, esters, or complexes.
 For example, tetracycline phosphate and
tetracycline hydrochloride equivalent to 250-mg
tetracycline base are considered pharmaceutical
alternatives.
 The FDA currently considers a tablet and capsule
containing the same active ingredient in the same
dosage strength as pharmaceutical alternatives.
 Therapeutic alternatives: Drug products
containing different active ingredients that are
indicated for the same therapeutic or clinical
objectives.
 Active ingredients in therapeutic alternatives are
from the same pharmacologic class and are
expected to have the same therapeutic effect when
administered to patients for such condition of
use.
 For example, ibuprofen is given instead of aspirin;
cimetidine may be given instead of ranitidine.