The pharmacokinetics of tiracizine, a new class I antiarrhythmic agent, and 3 of its metabolites were assessed in serum and urine of 8 healthy extensive metabolisers after single oral administration of 50, 100, and 200 mg tiracizine hydrochloride. Additionally, tiracizine induced ECG-changes were compared between the different doses. With increasing doses enhancement of AUC and C_max of tiracizine and its metabolites revealed a slight deviation from linearity indicated by exceeding the upper limits of the 95% nonparametric confidence interval set by 0.8-1.2 for the ratio (dose corrected parameters after the 100 and 200 mg dose, respectively)/(parameters after 50 mg). The increase of the dose corrected parameters after the 200 mg dose was about 1.3-fold compared with the 50 mg parameters for the parent compound as well as its metabolites. The significant decrease of the renal clearance of all 4 substances with increasing doses indicates that saturable tubular secretion mainly accounts for non-linearity. Due to the occurrence of non-linear (tubular secretion) as well as linear (glomerular filtration, hepatic metabolism) elimination in parallel, however, it is concluded that saturable tubular secretion is of minor importance at higher doses and should not be overestimated. However, there was some evidence for saturable hepatic tiracizine metabolism in 4 of the 8 participants. Therefore, a fall of apparent intrinsic clearance has also to be taken into consideration, especially at higher doses. PQ- and QRS-intervals were prolonged in a dose dependent manner and culminated at 1 h after drug intake. QT_c-time, however, remained unchanged. A log-linear relationship between serum concentrations of the parent compound and PQ- and as well as QRS-time is suspected for serum levels about 80 ng/ml, but has to be confirmed by individual pharmacokinetic-pharmacodynamic modelling. PQ- and QRS-intervals might be suitable for tiracizine therapeutic monitoring.