A versatile computational method for the determination of areas under the curve and moment curve following multidose drug administration

The accurate determination of area under the biologic fluid concentration-time curve (AUC) and area under the first moment curve (AUMC) are important in the calculation of a compound's pharmacokinetic parameter estimates. Although numerous mathematical methods exist for the calculation of both AUC and AUMC under varying conditions, some permit direct computation of areas, whereas others only approximate the true areas. In this study, we describe an alternative mathematical method which allows the direct calculation of either the AUC or AUMC after any dose of drug administered by any route. Simulated data with known areas were used to assess the accuracy of the proposed method and compared to area calculations obtained from widely used published methods. Experiments were also performed under conditions of varying elimination half-lives and reduced numbers of concentration-time values. Under any experimental condition, the newly proposed method was the most accurate in determining both the AUC and AUMC. Percent deviations from exact area values were ≤0.11% with the proposed method, whereas as much as 30% deviation was observed using other methods of calculation. These findings support the accuracy of the proposed method in calculating the AUC or AUMC and its utility in data analysis.