Abstract
The objective of this study was to clarify the relationship between the pharmacokinetic parameters of telmisartan and the occurrence of adverse events. In order to perform this study, a total of 1500 adverse events was collected from the eight clinical trials performed in Europe and the United States and the pharmacokinetic parameters (Cmax and AUC) were calculated with the parameters obtained from the population pharmacokinetic model which we have built. Using these data, the pharmacokinetic parameters (Cmax and AUC) were compared between subjects with or without the occurrence of adverse events. The Mann-Whitney test was performed to analyze ten adverse events selected based on the order of frequency. For eight of these ten adverse events, no significant between-group difference was observed in any pharmacokinetic parameter. For two adverse events, pain and sinusitis, the pharmacokinetic parameters, Cmax and AUC, were greater in subjects with adverse events as compared with those without adverse events, but the intersubject variability of pharmacokinetic parameters was large and there were many subjects in whom Cmax and AUC were high without any adverse event. These results suggest that there is no clear relationship between pharmacokinetic parameters of telmisartan and the occurrence of adverse events.
