Bioavailability and Bioequivalence

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1. Bioavailability

1.4. Absolute Bioavailability

Bioavailability is calculated by comparing plasma levels of a drug given via a particular route of administration (for example, orally) with plasma drug levels achieved by IV injection. This is where the AUC comes into play (the area under the curve calculated by plotting plasma concentrations of the drug versus time). The AUC equals the total exposure to an API that the body receives. In brief, the mathematical concept of Dost's Law of Corresponding Areas(1972) relates the AUC of an IV dose to the AUC of an orally administered dose. If the area under the oral concentration curve covers 50% of the area covered by the IV curve, the law dictates that the drug is 50% bioavailable.

concentration vs time

Figure 4: Concentration vs. time graph of AUC of IV and oral administration of a medicine

The bioavailability of the intravenous dose of any drug is by definition 100%. Hence, the bioavailability of all other formulations and routes of administration can be compared to this reference value as an absolute standard, and from this the equation for absolute bioavailability can be derived:

The absolute bioavailability then is the dose-corrected area under the curve (AUC) non-intravenous divided by AUC intravenous. The equation for calculating the absolute bioavailability (denoted by the letter f or, if expressed in percent, by F), of a drug administered orally (tablet) is given below:

graph 1