Characterization of drug disposition and dosing using bioelectrical impedance.

Abstract

Bioelectrical impedance analysis (BIA) yields accurate, safe and non-invasive estimates of body composition in humans. Pharmacokinetic characterization of drugs represents the body as a series of non-physiologic compartments. We evaluated the utility of BIA in the pharmacokinetic characterization and dosing of water soluble drugs. Serial serum concentrations of gentamicin (G) in 30 hospitalized adults, and theophylline (T), in 15 normal adult males were obtained over a dosing interval after an 8h fast, and analyzed in duplicate by enzyme-mediated immunoassay technique. BIA was performed serially in duplicate during the same time period using a fixed frequency (50kHz, 800 microA) current-injection 4-electrode plethysmograph. Multiple regression techniques were used to develop descriptive models of pharmacokinetic parameters which yielded equations with p-values < 0.03 and coefficients of variation < 20% accounting for > 85% of the pharmacokinetic variability. The G models were then tested in 20 critically ill adults at steady state by serum concentration measurement (criterion standard) and BIA. BIA predictive equations yielded pharmacokinetic parameters not different (by paired t-tests) than those derived by serum concentration measurement. While BIA is an innovative approach to the non-invasive characterization water soluble drugs, further testing with variable frequency BIA under perturbed conditions is warranted.