9.3: Bioavailability Study Design: Absolute Versus Relative Bioavailability

Bioavailability is a crucial pharmacokinetic parameter that quantifies the proportion of an administered drug that reaches the systemic circulation and is available for therapeutic action. Regulatory agencies mandate the assessment of bioavailability, typically measured as the area under the drug plasma concentration-versus-time curve (AUC), to ensure the efficacy and safety of pharmaceutical products. These evaluations are categorized as absolute and relative bioavailability studies.

Absolute bioavailability (F_abs) compares the systemic drug exposure achieved through extravascular administration, such as oral or subcutaneous routes, relative to intravenous administration, which is considered to provide 100% bioavailability. It is calculated as the dose-normalized ratio of the extravascular AUC to the intravenous AUC. For oral drugs, F_abs range from 0 to 1, corresponding to 0% to 100% systemic absorption. Factors influencing F_abs include the drug's physicochemical properties, first-pass metabolism, and permeability across biological membranes. This measure is critical for determining drug delivery efficiency through non-intravenous routes.

Relative bioavailability (F_rel) evaluates the systemic drug exposure provided by a test formulation compared to a reference formulation. It is computed as the ratio of their respective AUCs, normalized for dose. F_rel studies are essential in assessing the performance of new formulations, generic drugs, and alternative delivery systems. Consistent relative bioavailability ensures therapeutic equivalence between formulations, maintaining clinical efficacy and safety profiles.

Beyond formulation comparisons, bioavailability studies also address critical pharmacological concerns such as food-drug interactions and drug-drug interactions. These studies examine how food intake or concurrent medications influence the oral drug's systemic availability. Such evaluations guide recommendations on dosing regimens and co-administration practices, optimizing therapeutic outcomes and minimizing adverse effects.

Understanding and quantifying bioavailability are indispensable for drug development, regulatory approval, and clinical application, ensuring that pharmaceutical products achieve their intended therapeutic goals.

The bioavailability data measured by the area under the drug plasma concentration-versus-time plot is mandatory for regulatory submissions.

These studies provide absolute and relative bioavailability.

Absolute bioavailability measures the proportion of active drug in the systemic circulation after an extravascular administration compared to the intravenous route, which represents 100% bioavailability.

It is the ratio of dose-corrected extravascular drug AUC to the intravenous drug AUC. For oral drugs, F_abs is computed as follows. Here, an F_abs range of 0 to 1 represents a systemic absorption rate of 0 to 100%.

Relative bioavailability assesses the systemic exposure of a drug in a test formulation against a reference formulation. F_rel compares the area under the curves of both formulations as seen in the equation.

Such studies ensure new formulations have consistent systemic drug bioavailability compared to approved formulations already in use.

Additionally, they characterize food effects and drug-drug interactions by determining the oral drug’s bioavailability with and without food or the interacting drug.