Serum and urine kinetics of unchanged tiracizine (T), a new class I antiarrhythmic agent, and three metabolites (M1, 2, and 3) were assessed in eight healthy extensive metabolizers after a single oral administration of 50 mg tiracizine and during steady state (50 mg b.i.d.). Additionally, tiracizine‐induced ECG changes were measured. Considerable accumulation of M1 and M2 was observed during repeated dosing (M1, C_max,ss = 391.8 ng mL⁻¹ against C_max,sd = 132.8 ng mL⁻¹; M2, C_max,ss = 143.2 ng mL⁻¹ against C_max,sd = 25.8 ng mL⁻¹). However, significant increases of AUC (AUCτ = 261.9 ng h mL⁻¹ against AUC_0–∞,sd = 182.9 ng h mL⁻¹), C_max (C_max,ss = 75.9 ng mL⁻¹ against C_max,sd = 56.9 ng mL⁻¹) and t_1/2β (t_1/2β,ss = 4.0 h against t_1/2β,sd = 2.4 h) of the parent compound indicate non‐linear kinetics. The significant decrease in renal clearance of all four substances as well as the decrease of non‐renal tiracizine clearance with repeated dosing led to the assumption that non‐linearity is due to saturable renal excretion and a fall in intrinsic tiracizine clearance. PQ time was prolonged significantly during steady state and culminated at the t_max of the parent compound, whereas there was no change in any ECG parameter after a single‐dose administration of 50 mg tiracizine.