Bioavailability

Dr. Hiba Algaali Altayeb

• Bioavailability is the fraction of administered drug that
reaches the systemic circulation unchanged.

• For example, if 100 mg of a drug are administered orally,

and 70 mg of this drug are absorbed unchanged (and reach
circulation), the bioavailability is 70 percent.

• Determining bioavailability is important for calculating drug

dosages for non-intravenous routes of administration .
• Bioavailability is determined by comparing plasma levels of a drug after a particular
route of administration (e.g

• , oral administration) with levels achieved by IV administration.

• After IV administration, 100% of the drug 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, the area under the curve
(AUC) can be measured.

• Bioavailability of a drug given orally is the ratio of the AUC for oral administration to
the AUC following IV administration (assuming IV and oral doses are equivalent).
Factors influencing systemic
availability
Pharmaceutical factors: (formulation of the drug)
• The amount of drug that is released from a dose form (tablet,
capsule, syrup, Suppository) and so becomes available for

absorption is referred to as its bioavailability.

• This is highly dependent on its pharmaceutical formulation.

• {Some definitions of enteral dose-forms:
Tablet: a solid dose form in which the drug is compressed
with pharmacologically inert substances (excipients)}
• With tablets, for example, particle size (surface area exposed
to solution), diluting substances, tablet size and pressure used
in the tabletting machine can affect disintegration and
dissolution and so the bioavailability of the drug.
• Manufacturers must test their products to ensure that
their formulations release the same amount of drug
at the same speed from whatever manufactured
batch or brand the patient may be taking.

Different shapes but same

drug with same
bioavailability
• Differences in bioavailability are prone to occur with modified-release
(m/r) formulations, i.e. where the rate or place of release of the active
ingredients has been modified (also called sustained, controlled or
delayed release).

• Modified-release preparations from different manufacturers may differ in

their bioavailability profiles despite containing the same amount of drug,
i.e. there is neither bioequivalence nor therapeutic equivalence.

• When prescribing drugs rugs with narrow therapeutic ratio like m/r
preparations of theophylline, lithium, nifedipine, digoxin and diltiazem,
it is better to prescribe particular brand name for a particular patient.
• Substantial differences in bioavailability of digoxin tablets (a drug used in the
treatment of heart failure and atrial fibrillation) from one manufacturer occurred when only
the technique and machinery for making the tablets were changed;

• also tablets containing the same amount of digoxin but made by

different companies, were shown to produce different plasma
concentrations and therefore different effects, i.e. there was no
bioequivalence nor therapeutic equivalence.
• Physicians tend to ignore pharmaceutical formulation as a factor in variable or
unexpected responses because they do not understand it and feel entitled to rely on
reputable manufacturers and official regulatory authorities.
Biological factors

• Biological factors related to the gut include:

limitation of drug absorption by drug transporter systems

destruction of drug by gastric acid, e.g. benzylpenicillin, and

impaired absorption due to rapid intestinal transit

• Drugs may also bind to food constituents, e.g. tetracyclines to

calcium (in milk) and to iron, or to other drugs (e.g. acidic drugs to
colestyramine) and the resulting complex is not absorbed.
Presystemic (first-pass) elimination
(First-pass hepatic metabolism)

• When a drug is absorbed across the GI tract, it first

enters the portal circulation before entering the
systemic circulation

• If the drug is rapidly metabolized in the liver or gut wall

during this initial passage, the amount of unchanged
drug entering the systemic circulation is decreased. This
is referred to as first-pass metabolism
• This is a significant feature of the oral route, and as little as 10-20% of the

parent drug may reach the systemic circulation unchanged.

• Drugs that exhibit the hepatic first-pass phenomenon do so because of

the rapidity with which they are metabolised.

• These drugs should be given in high doses to cause the desired action.

• First-pass metabolism by the intestine or liver limits the efficacy of many

oral medications. For e.g. more than 90% of nitroglycerin is inactivated

• Hence, it is primarily administered via the sublingual, transdermal, or

intravenous route.
 Solubility of the drug
• Very hydrophilic drugs are poorly absorbed(they can not
cross lipid-rich cell membrane).

• drugs that are extremely lipophilic are also poorly absorbed,

because they are insoluble in aqueous body fluids and,
therefore, cannot gain access to the surface of cells.

• For a drug to be readily absorbed, it must be largely

lipophilic, yet have some solubility in aqueous solutions.
What is the meaning of bioequivalence?
• Two related drug preparations are bioequivalent if they
show comparable bioavailability and similar times to
achieve peak blood concentrations


What is Therapeutic equivalence?

• Two drug formulations are therapeutically equivalen if they are

pharmaceutically equivalent (i.e., they have the same dosage
form, contain the same active ingredient at the same strength,
and use the same route of administration) with similar clinical
and safety profiles.

• Thus, therapeutic equivalence requires that drug products are

bioequivalent and pharmaceutically equivalent
• References:
• Bennett &Brown clinical pharmacology 11th edition.
• Lippincott’s clinical review of pharmacology 7th
editon.