Relationship of Bioelectrical Impedance to Pharmacokinetic Parameters of Theophylline in Healthy Males

Abstract

Bioelectrical impedance is a reliable, safe, non-invasive and valid method of determining body composition, using measures of resistance and reactance by passing a low voltage alternating current through the body. This study investigates relationships between the pharmacokinetics of theophylline and parameters of bioelectrical impedance in 15 nonsmoking, healthy, adult male volunteers. After an overnight fast, subjects received 5 mg/ kg of aminophylline intravenously over 30 minutes. Blood samples were obtained serially over a period of 12 hours. Bioelectrical impedance measurements were made in triplicate, using a 4-electrode plethysmograph. Sera were assayed in duplicate by enzyme-mediated immunoassay (coefficient of variation < 5%), and data were fitted to a non-compartmental regression program. An all-subsets multiple-regression technique was employed to arrive at predictive equations for theophylline clearance (CL) and volume of distribution at steadystate (V_ss) using age, height, weight and mean bioelectrical impedance parameters. Equations for V_ss and CL revealed p-values of < 0.001 and coefficients of variation of 8.5 and 13.33%, respectively. Although the equations display some degree of collinearity, they account for 95 and 86.5% of the variability in V_ss and CL, respectively, and represent an innovative approach to the estimation of pharmacokinetic parameters.