whereEHis the hepatic extraction ratio. Therefore, leads with high hepatic
extraction values (EH~1) will seldom reach the general circulatory system in
sufficient quantity to be therapeutically effective if administered orally.
Bioavailability studies using animals are used to compare the efficiency of the
delivery of the dosage forms of a drug to the general circulatory system as well
as the efficiency of the route of administration for both licensed drugs and new
drugs under development. Two useful measurements arerelativeandabsolute
bioavailability.
Relative availability. Relative bioavailability may be used to compare the
relative absorptions of the different dosage forms of the same drug and also
the relative availabilities of two different drugs with the same action when
delivered using the same type of dosage form. It is defined for equal doses as:
relative bioavailability ¼
AUC for drug A (or dosage form A)
AUC for drug B (or dosage form B)
(8:26)
Percentage relative bioavailability figures may be obtained by multiplying
Equation (8.26) by 100. A correction must be made if different drug doses are
used, in which case Equation (8.26) becomes:
relative bioavailability ¼
(AUC for drug A or dosage form A)=dose A
(AUC for drug B or dosage form B)=dose B
(8:27)
A relative bioavailability value significantly higher than unity would suggest
that the bioavailability of the drug from the dosage form A is much better than
that from the dosage form B, whilst a value significantly less than unity would
indicate that the reverse was true.
This type of calculation is useful in drug design as it ensures that the dosage
forms used in trials are effective in delivering the drug to the general circulation.
It is also used by licensing authorities as a check on the efficacy of products
when manufacturers change the dosage form of a drug in clinical use.
Absolute bioavailability. Absolute bioavailability is used as a measure of the
efficiency of the absorption of the drug. It is defined in terms of the total dose of
the drug the body would receive if the drug were placed directly in the general
circulation by an I.V. bolus injection, that is:
absolute bioavailability(F)¼
AUC for oral dosage form=oral dose
AUC for IV dosage form=IV dose
(8:28)
Comparison of the absolute bioavailabilities of analogues enables the medi-
cinal chemist to select the analogue that would be most likely to give the
EXTRAVASCULAR ADMINISTRATION 173