Bioimpedance Assessment of Antipyrine Pharmacokinetics before and after Enzyme Induction

Abstract

Bioimpedance (BI) technology, a noninvasive method of measuring body composition, has been previously used to develop a predictive model for metabolic clearance under basal conditions. The present investigation was conducted to assess the ability of BI-derived models to predict drug disposition in a perturbed system. An antipyrine pharmacokinetic and impedance analysis of 15 healthy male subjects was performed before and on the 14th day of phenobarbital administration (i.e., after enzyme induction). The all subsets multiple regression technique was used to develop preinduction models for clearance (Cl), (p = 0.021, R² = 0.654) and volume of distribution at steady-state (V_d ^ss) (p = 0.001, R² = 0.867), using demographic and mean BI parameters. The preinduction Cl model significantly underestimated postinduction measurements and was not predictive of changes in CI. The preinduction V_d ^ss model was predictive of postinduction V_d ^ss. It appears that the BI-derived model is unable to predict perturbations in metabolic clearance caused by enzyme induction.