A New Method for the Estimation of Absorption Rate Constant in Two-Compartment Model by Extravascular Administration

Abstract

This article describes a new method of estimating the absorption rate constant (k_a) of a 2-compartment model with extravascular administration, which is called an alternative method. The method was based on approximating the distribution and elimination phases of a 2-compartment model to the elimination phase of a one-compartment model. By using the model equation t_max=lnk_a-ln(k₁₀+k₁₂)k_a-(k₁₀+k₁₂), first, we obtained the peak time (t_max) and the sum value of the first-order elimination rate constant (k₁₀) and the distribution rate constant (k₁₂), then the iterative method was used to obtain estimated value. And the estimation results were compared with the results obtained by the Loo-Riegelman and statistical moment methods and the factors affecting the estimation results of alternative method were explored. Finally, verification experiments were carried out with actual data in the literature. In general, a good estimation effect on the value of k_a in the extravascular administration of the 2-compartment model was obtained by this method, with less errors compared with the commonly used 2 other methods (p < 0.05). Changes in k₁₂, k₁₀, k_a, and another distribution rate constant (k₂₁) all influenced the estimation results. The alternative method also showed good results in estimating k_a of compounds in the literature.

Keywords: Loo-Riegelman method; absorption rate constant; alternative method; statistical moment method.