The acute effects of daily nicotine intake on heart rate – a toxicokinetic and toxicodynamic modelling study

Abstract

Joint physiologically-based toxicokinetic and toxicodynamic (PBTK/TD) modelling is applied to simulate concentration-time profiles of nicotine, a well-known stimulant, in the human body following single and repeated dosing. Both kinetic and dynamic models were first calibrated by using in vivo data from the literature. The models were then used to estimate the blood and liver concentrations of nicotine in terms of the Area Under Curve (AUC) and the peak concentration (Cmax) for selected exposure scenarios based on inhalation (cigarette smoking), oral intake (nicotine lozenges) and dermal absorption (nicotine patches). The model simulations indicate that whereas frequent cigarette smoking gives rise to high AUC and Cmax in blood, the use of nicotine-rich dermal patches leads to high AUC and Cmax in the liver. Venous blood concentrations were used to estimate one of the most common acute effects, mean heart rate, both at rest and during exercise. These estimations show that cigarette smoking causes a high peak heart rate, whereas dermal absorption causes a high mean heart rate over 48 hours. This study illustrates the potential of using PBTK/TD modelling in analysing the safety of nicotine-containing products.