Purpose: The muscarine receptor antagonist propiverine in immediate release tablet form (IR) undergoes presystemic elimination mediated by CYP450 enzymes and intestinal efflux transporters. The aim of our study with propiverine IR and extended release (ER) was to determine whether propiverine disposition is dose linear, to compare the pharmacokinetics of propiverine in oral solution with IR and ER and to show how absorption rate is associated with bioavailability. Methods: The pharmacokinetics of propiverine administered as intravenous propiverine (15 mg), 10, 15, and 30 mg propiverine IR, an oral propiverine solution (15 mg) and 10, 15, 30, and 45 mg propiverine ER were measured in two randomized, controlled, single-dose, five-period, cross-over studies, with each case involving a study cohort of ten healthy Caucasian subjects. Results: Disposition of propiverine IR and ER was not dose-related. The bioavailability of ER was 64.5±16.1% compared to 50.3±13.4% (non-significant) after administration of the IR and propiverine solution (42.6±14.8%, p<0.05). The mean absorption time (MAT) of ER (14.2±4.79 h) was significantly longer than that of the solution and IR (3.94±4.14 and 0.38±3.79 h, respectively; both p<0.05). The bioavailability of propiverine was significantly correlated to the MAT (r=0.521, p<0.001). Renal excretion of the metabolite M-23 after propiverine ER administration (6.7±2.7%) was significantly lower than that after administration of the oral solution (10±2.2%) and of IR (9.8±2.7%; both p<0.05). Conclusions: The bioavailability of propiverine appears to be dependent on the intestinal site of dissolution and, consequently, on the extent of presystemic intestinal elimination.