F (absolute bioavailability) / Frel (relative bioavailability)
units
Percent (%) or dimensionless fraction (0 to 1.0)
equation
F = (AUC_extravascular / Dose_extravascular) / (AUC_IV / Dose_IV) = fa · fg · fh
pioneer
Biopharmaceutics and clinical bioequivalence standards
Core Principles & Analysis
By definition, an intravenous (IV) bolus dose has an absolute bioavailability of F = 1.0 (100%); for an oral dose, F is measured experimentally by comparing the dose-normalized plasma Area Under the Curve (AUCoral) to the intravenous AUCIV in a crossover study.
Oral bioavailability is the product of three sequential survival fractions: the fraction absorbed across the intestinal epithelium (fa), the fraction escaping gut-wall CYP3A4 metabolism and P-gp efflux (fg), and the fraction escaping first-pass portal hepatic extraction (fh = 1 − EH).
Regulatory bioequivalence testing for generic oral tablets requires demonstrating that the 90% confidence intervals for the geometric mean ratios of both peak concentration (Cmax) and total exposure (AUC) fall within 80% to 125% of the reference innovator formulation.