[Biological availability and pharmacodynamics following single oral administration or three different...

The bioavailability of 3 different commercial available isosorbide mononitrate (IS-5-MN; CAS 16051-77-7) 40 mg slow-release preparations (A, B and reference formulation C) was determined after oral application to 18 healthy volunteers in a randomized cross-over study. The AUC after C (26.9 mumol/l x h) was not significantly different from that for A (25.1 mumol/l x h) and B (26.0 mumol/l x h). The corresponding 95% confidence intervals were within the limits of 80-120%. Maximal plasma concentrations (Cmax) for C (1.90 mumol/l), A (1.91 mumol/l), and B (2.05 mumol/l) were obtained at (tmax) 5.72 h, 4.94 h and 4.72 h, respectively. The 95% confidence intervals for Cmax and tmax were within the prescribed limits of 70-130%. Mean residence times (MRT) 10.5 h (C), 10.3 h (A), and 10.1 h (B) and plateau-times (duration over which the plasma concentration greater than 0.524 mumol/l) 17.8 h (C), 17.1 h (A), and 17.0 h (B) were not significantly different. It is concluded that the test preparations A and B are bioequivalent to reference C. Systolic blood pressure and heart rate, easily measurable indeces of the pharmacodynamic effects, showed no significant differences between the 3 preparations. In agreement with recently published data, plasma concentrations above 1.5 mumol/l did not result in a further reduction of systolic blood pressure, but were associated with a further marked elevation in heart rate.