Bioavailability

By: Kainat Gul

Bio-availability

• Bio-availability is defined as rate

and extent of absorption of
unchanged drug from its dosage
form and become available at the
site of action.
• Rate and extent at which
therapeutically drug reaches
systemic circulation.
• A measure relative to some
standard of rate & amount of drug,
which reaches the systemic
circulation unchanged following
the administration of dosage form.
Types of Bioavailability

Relative Bioavailability (Fr): If

Absolute Bioavailability (F): If
the systemic availability of a
the systemic availability of a
drug administered orally is
drug administered orally is
determined by doing its
determined by doing its
comparison with that of an oral
comparison with I.V.
standard of the same drug, it is
administration, it is known as
known as a relative
absolute bioavailability.
bioavailability.
• Range of Bioavailability – 0 to 1.
• It is usually expressed as percentages (%).
• An absolute bioavailability of 1 (or 100%) indicates complete absorption.
• Relative bioavailability of 1 (or 100%) implies that the bioavailability of drug from both
the dosage forms is the same but does not indicate the completeness of the systemic drug
absorption.
• Drugs having 100% bioavailability.
• Drugs having 100% bioavailability include chlordiazepoxide, diazepam, lithium,
metronidazole, phenobarbitol, salicylic acid, trimethoprin and valproic acid.
Determination of
bioavailability
• Bioavailability is determined by
comparing plasma levels of a drug after a
particular route of administration (for
example, oral administration) with plasma
drug levels achieved by IV injection in
which all of the agent rapidly enters the
circulation. When the drug is given orally,
only part of the administered dose appears
in the plasma.
• By plotting plasma concentrations of the drug versus time, we
can measure the area under the curve (AUC).
• This curve reflects the extent of absorption of the drug. [Note:
By definition, this is 100 percent for drugs delivered IV].
• Bioavailability of a drug administered orally is the ratio of the
area calculated for oral administration compared with the area
calculated for IV injection.
• Bioavailability (the rate and extent of drug absorption) is
generally assessed by the determination of following three
parameters. They are :
• Cmax (Peak plasma concentration).
• tmax(time of peak).
• Area under curve.
•  AUC: Is the measurement of the extent of the drug
bioavailability It is the area under the drug plasma
level-time curve from t =0 & t = ∞ and is equal to the
amount of unchanged drug reaching the general
circulation divided by the clearance.
• Cmax: (Peak plasma drug concentration)
• Maximum concentration of the drug obtained after
the administration of single dose of the drug.
• Expressed in terms of μg/ml or mg/ml.
• tmax: (Time of peak plasma concentration)
• Time required to achieve peak concentration of the
drug after administration.
• Gives indication of the rate of absorption.
• Expressed in terms of hours or minutes.
Factors That
Influence Bioavailability
1.First-pass hepatic metabolism: When a
drug is absorbed across the GI tract, it enters
the portal circulation before entering the
systemic circulation. If the drug is rapidly
metabolized by the liver, the amount of
unchanged drug that gains access to the
systemic circulation is decreased.
• Many drugs, such as propranolol or
lidocaine, undergo significant
biotransformation during a single passage
through the liver.
2- Clinical Significance:
• Bioavailability differs with the dosage forms. Drug in liquid form
have more bioavailability than those of solids, while gases have the
highest bioavailability. This is why inhalation is used in bronchial
asthma.
• With the same brand, dosage form manufactured by different
companies may differ in bioavailability.
• Three terms are generally used:
a.Bioequivalence: Two related drugs are bioequivalent if they show
comparable bioavailability and similar times to achieve peak blood
concentrations.
• Two related drugs with a significant difference in bioavailability are
said to be bioinequivalent.
• Therapeutic equivalence: Two similar drugs are therapeutically
equivalent if they have comparable efficacy and safety.
• Clinical effectiveness often depends on both the maximum serum
drug concentrations and on the time required (after administration) to
reach peak concentration. Therefore, two drugs that are bioequivalent
may not be therapeutically equivalent.
b.Therapeutic equivalent
• If two similar drugs perform the same effect, have
same efficacy and toxicity, then they are called
therapeutically equivalent.
• It indicates that two or more drug products that
contain the same therapeutic active ingredients elicit
same pharmacologic effects and can control the
disease to the same extent.
c. Chemical Equivalent
•  Chemical equivalence: two or more formulations
contain the same labelled chemical substance as an
active ingredient in the same amount.
3. Route of administration
• Drugs given by intravenous route have 100% bioavailability. Exception includes
prostaglandins, which are inactivated/metabolized in the lungs, therefore, their
bioavailability may be zero after I/V injection. Those given by intramuscular route
have bioavailability less than I/V route but more than subcutaneous route, while
subcutaneous route has bioavailability more than the oral route.
• Only 10% of the dose of digoxin reaches systemic circulation after oral administration
because of lack of absorption and bacterial metabolism within intestines. Even some of
the drugs given by oral route may have 100% bioavailability but this is rare.
• By rectal route, half of the drug undergoes first pass metabolism.
• Chloramphenicol, an antibiotic, administered by intravenous route has bioavailability
less than oral route because it is present in pro form and has to be activated in the
intestines.
4. Chemical Instability
• Drug may be destroyed by the HCl or enzymes present in the GIT. Benzyl penicillin is
not given orally because it is destroyed by HCl. Parenteral route is generally preferred.
Therapeutic Index:
• Therapeutic index represents the safety of a drug. Drugs having large therapeutic index
and  safer and vice versa.
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