Impulsive Feedback Modeling of Levodopa Pharmacokinetics Subject to Intermittently Interrupted Gastric Emptying*

Abstract

A novel modeling approach capturing the multiple peak phenomenon in oral levodopa administration is proposed. Multiple peaks in the blood plasma concentration of the drug are attributed to the effects caused by gastric emptying. The developed model describes the instances of interrupted gastric emptying by an impulsive feedback of the dopamine concentration in the brain acting on the pyloric sphincter. A combination of the continuous levodopa clearing dynamics and the impulsive feedback results in a hybrid model, whose solutions are positive and bounded. The stability properties of the model are studied by means of a Poincaré map describing the propagation of the continuous model states through the firings of the impulsive feedback. Model feasibility is illustrated on data sets obtained in clinical experiments.