B-Intercept

The intercept with the Y-axis of the elimination portion of a plot of plasma concentration versus time data for a drug that follows two compartment kinetic behaviour. This (theoretical) value on the Y-axis (concentration axis) is nominally equal to the theoretical concentration of drug in the plasma at time = 0 if drug distribution was complete (i.e. if distribution occurred instantaneously) but there had not yet been any elimination from the body. In other words, the entire dose of the drug is distributed between plasma and tissues and we have reached an equilibrium, but no drug has yet been lost to elimination.

An apparent volume of distribution value can be calculated from the dose divided by the B-intercept. This AV_D value (for a two compartment drug) is referred to as the extrapolated apparent volume of distribution (AV_{D extrap}) which typically over-estimates the volume to the extent that, clinically, this value is not very useful.

The over-estimation results from the fact that during the terminal elimination phase, the slow redistribution of drug from tissues back to plasma increases the tissue:plasma concentration ratio from that existing at steady state, so that drug in the body appears to be distributed throughout a larger total volume. As a result, unchanged clearance of a larger apparent volume corresponds to a smaller elimination rate constant (β), which is reflected in a reduced slope for the terminal elimination portion. Back-extrapolation of this reduced-slope line to the Y-axis at t=0 yields an intercept (B-intercept) that is anomalously low, confirming the high estimate, from Dose/B, of AV_D.

As an illustration of this phenomenon, if a dose of 500 mg was administered IV and the B-intercept was 4mg/litre (see figure), the calculated AV_{D extrap} would be 125 litres. The AUC of the concentration versus time plot, calculated with graphing software from the same data plotted on a linear concentration axis (inset), is 533.1 mg/l min. With a value for β calculated from the terminal slope as 0.0116 min^-1 (see entry for beta (β) rate constant), the AV_{D area} can be calculated from Dose/(AUC × β) (see entry for apparent volume of distribution) to be 81 litres. This is only 65% of the value calculated for AV_{D extrap}.