Modeling population pharmacokinetics of lidocaine - Should cardiac output be included as a patient factor?

Background: Inclusion of cardiac output and other physiologic parameters, i n addition to or instead of, demographic variables might improve the popula tion pharmacokinetic modeling of Lidocaine. Methods: Thirty-one patients were included in a population pharmacokinetic study of lidocaine. After bolus injection of lidocaine (1 mg/kg), 22 or 10 blood samples per patient were taken from a radial artery. During the exper iment, cardiac output was measured using a thoracic electrical bioimpedance method. The following four population pharmacokinetic models were construc ted and their performances investigated: a model with no covariates, a mode l with cardiac output as covariate, a model with demographic covariates, an d a model with both cardiac output and demographic characteristics as covar iates. Model discrimination was performed with the likelihood ratio test. Results: inclusion of cardiac output resulted in a significant improvement of the pharmacokinetic model, but inclusion of demographic covariates was e ven better. However, the best model was obtained by inclusion of both demog raphic covariates and cardiac output in the pharmacokinetic model. Conclusions: When population pharmacokinetic models are used for individual ization of dosing schedules, physiologic covariates, e.g.., cardiac output, can improve their ability to predict the individual kinetics.