Pharmacokinetic-pharmacodynamic Modelling of Side Effects of Nitrendipine

The modelling aim in this study was to explore the relationship between plasma concentrations of a cardiovascular drug nitrendipine and occurrences of its side effects. The data were taken from a bioequivalence study in 40 men with a 20 mg single dose of nitrendipine. During the study occurrences of side effects, their severity, onset time and duration were recorded. Overall, side effects occurred in 26 applications. A two compartment pharmacokinetic model with lag time and first order absorption was fitted to plasma concentrations. For a pharmacodynamic part fixed effect model was applied. An indirect link model based on effect compartment was used to connect the pharmacokinetic and pharmacodynamic data. Estimated model parameters of a group with side effects and a group without them were compared. Increased extent and rate of absorption raised the probability for occurrence of side effect. Incidence of side effect was also determined by increased sensitivity to nitrendipine at the site of action.