Area-based estimation of the initial volume of distribution and elimination rate constant following intravenous bolus injection.

We evaluate here an area term, the area under the rate of change of concentration-time curve (AURC), which allows the determination of the initial or central volume of distribution (V1). It has previously been shown that AURC is equal to the sum of the coefficients of a multiexponential equation and, therefore, V1 = dose/AURC. It is also shown that the normalized moment, AURC/AUC, is equal to the elimination rate constant, K10, where AUC is the area under the concentration-time curve. This area-based method to estimate V1 and K10 has been evaluated with simulation of three model equations and compared with nonlinear regression analysis of the same data. Random errors of 10 and 15% were introduced into the concentration values. The AURC method provides values of both parameters that are similar to those obtained from nonlinear regression analysis and which are reasonably accurate estimates of the theoretically correct values. The potential limitations of this area method are discussed. Good correlations were also observed for values of V1 and K10 obtained by AURC and regression methods for data obtained from the literature for 13 different drugs.