Purpose of BABE

CHU YUAN SHAN

•Bioavailability and bioequivalence studies are important in the process of
approving pharmaceutical products for marketing.

•Bioavailability is defined as the rate and extent to which the active

ingredient or active moiety is absorbed from a drug product and becomes
available at the site of action .

•Bioavailability data provide :

an estimate of the fraction of drug absorbed from the formulation

information about the pharmacokinetics of the drug.

• Relative bioavailability studies compare two drug product formulations.

•Bioavailability studies are drug product performance studies used to define
the effect of changes in the physicochemical properties of the drug
substance, the formulation of the drug, and manufacture process of the drug
product (dosage form).
•A bioequivalence study is a specialized type of relative bioavailability
study.

•Bioequivalence is defined as the absence of a significant difference in the

rate and extent to which the active ingredient or active moiety becomes
available at the site of drug action when administered at the same molar
dose under similar conditions in an appropriately designed study.

•Bioequivalence studies are used to compare the bioavailability of the same

drug (same salt or ester) from various drug products.

•Bioavailability and bioequivalence can be considered as performance

measures of the drug product in vivo.

•If the drug products are pharmaceutically equivalent, bioequivalent, and

therapeutically equivalent (as defined by the regulatory agency such as the
FDA), then the clinical efficacy and the safety profile of these drug
products are assumed to be similar and may be substituted for each other.
RELATIVE AND ABSOLUTE AVAILABILITY

• For systemically available drug products, bioavailability is most

often assessed by determining the area under the drug plasma
concentration-versus-time profile (AUC).

• The AUC is considered the most reliable measure of a drug’s

bioavailability, as it is directly proportional to the total amount of
unchanged drug that reaches the systemic circulation.
Absolute Bioavailability
•Absolute bioavailability compares the bioavailability of the active drug in the
systemic circulation following extravascular administration with the
bioavailability of the same drug following intravenous administration

•Intravenous drug administration is considered 100% absorbed. The route of

extravascular administration can be inhaled, intramuscular, oral, rectal,
subcutaneous, sublingual, topi- cal, transdermal, etc.

•The absolute bioavailability is the dose-corrected AUC of the extravascularly

administered drug product divided by the AUC of the drug product given
intravenously.

•Absolute availability, Fabs, may be expressed as a fraction or as a percent by

multiplying Fabs  100. A drug given by the intravenous route will have an
absolute bioavailability of 100% (f = 1). A drug given by an extravascular route
may have an Fabs = 0 (no systemic absorption) and Fabs = 1.0 (100% sys- temic
absorption).
 Relative Bioavailability
•In a relative bioavailability study, the systemic exposure of a drug in a designated
formulation (generally referred to as treatment A or reference formulation) is
compared with that of the same drug administered in a reference formulation
(generally referred to as treatment B or test formulation).

•frequently included in regulatory submissions, the FDA recommends that new drug
developers rou- tinely use an oral solution as the reference for a new oral
formulation, for the purpose of assessing how formulation impacts bioavailability.

•used in drug development include studies to characterize food effects and drug–drug
interactions.

•used in developing new formulations of existing immediate-release drug products,

such as new modified-release versions or new fixed- dose combination formulations.

•commonly used for bridging formulations during drug development, for example, to
evaluate how drug systemic availability from a new premarket formulation compares
with that from an existing premarket formulation.