Modelling the Double Peak Phenomenon in pharmacokinetics

Two methods of modelling the Double Peak Phenomenon in pharmacokinetics are described; both are based on compartmental models. The first method assumes that the absorption of the drug from the gut to the systemic plasma varies with the location of the drug in the gut, with negligible absorption through the jejunum. It has the advantage of clear physiological interpretation, but there are a comparatively large number of parameters to be estimated. The second method assumes simultaneous input via two parallel pathways, and has been developed with the aim of reducing the number of parameters in the model. However, this approach lacks the direct relationship to physiology. The two methods are used to model two data sets provided by AstraZeneca and a further data set from the literature, describing the pharmacokinetics of veralipride. For all three data sets, the measurement is of concentration of drug in the systemic plasma following oral administration in solution form.