Area Under the Plasma Concentration Vs Time Curve

In the development of equations for the Wagner-Nelson method of calculation, the following equation was derived (see equation 42):

Amax2 f (Cpdt)2 0

This equation shows that the amounts of drug absorbed from two drug products (i.e., the relative bioavailability of product 1 compared with product 2) can be calculated as the ratio of the AUCs, assuming kel and Vd were the same in both studies.

If dosage form 2 (equation 42) is an IV dosage form, the absolute bioavailability of the extravascular dosage form (dosage form 1) is given by:

Absolute bioavailability _ AUCextravascular ,43

(extravascular dosage form) AUCIV (

The AUC for a plasma concentration versus time curve can be determined using the trapezoidal rule. For this calculation, the curve is divided into vertical segments, as shown in Figure 11. The top line of each segment is assumed to be straight rather than slightly curved, and the area of the segment is calculated as though it were a trapezoid; for example, the area of segment 10 is

The total AUC is then obtained by summing the areas of the individual segments.

It should be readily apparent that the trapezoidal rule does not measure AUC exactly. However, it is accurate enough for most bioavailability calculations, and the segments are chosen on the basis of the time intervals at which plasma was collected.

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