Calculating AUC

The AUC from Figure 3.3 can be calculated as shown in Table 3.1. However, in a number of instances, the decrease in concentration is not linear but rather exponential. A more accurate method for calculating AUC is to use a log trapezoidal rule. Two consecutive observations on the exponential curve C(i ) and C(i +i) at times tj and f(i+i) are related to each other by... 

Analogeous to the Cmax concentrations, the calculated AUC values in the milk were approx. 9 to 10 times higher than those in the blood. 

Area under the plasma/seruin/blood concentration-time curve from time zero to time t (AUCO-z), where t is the last sampling time point with a measurable concentration of the API in the individual formulation tested. The method of calculating AUC-values should be specified. In general AUC should be calculated using the linear/log trapezoidal integration method. The exclusive use of compartmental-based parameters is not recommended. 

The magnitude of change in K, K , or V due to lO is set to have a cv equal to 20%. A plot of calculated AUC versus dose (not shown) reveals the influence of lO variability on AUC, leading to a nonlinear relationship with dose. 

The simplest way to calculate AUC from measured plasma concentration data is to perform the linear regression analysis of In (Cp) versus < as in the previous section, then substitute the values of Cq and k derived from the intercept and slope into the equation... 

Figure 11.32 An example of a report (Excel format) for pharmacokinetic data obtained in an oral dose experiment using a pooled plasma strategy (six compounds analyzed per pooled plasma sample). The sample concentrations, the calculated AUC (area under the curve, a measure of bioavailabihty) and the time vs concentration plot for the dosed compound, are shown. Reproduced from Korfmacher, Rapid Commun. Mass Spectrom. 15, 335 (2001), with permission of John Wiley Sons Ltd.

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