EVALUATION OF THE PHARMACOKINETICS AND ABSOLUTE BIOAVAILABILITY OF 3 ISOSORBIDE-5-MONONITRATE PREPARATIONS IN HEALTHY-VOLUNTEERS

The objective of this study was two-fold: 1. to determine the pharmaco kinetic parameters and the bioavailability of two 20 mg isosorbide-5-m ononitrate (CAS 16051-77-7, IS-5-MN) preparations (treatments A and B) after single oral administration and 2. to evaluate the absolute bioa vailability of IS-5-MN, which was possible by the administration of a third IS-5-MN preparation (treatment C) by the intravenous route (1 mg /ml, dose 20 mg). The three preparations were examined in 24 healthy v olunteers according to a randomized 3-way, cross-over design, blood sa mples were withdrawn up to 24 h following the administration of IS-5-M N and plasma concentrations of IS-5-MN were quantified by a gas chroma tography method. The two oral preparations led to peak concentration v alues of about 360 ng/ml of IS-5-MN in the mean 0.90 h (treatment A) a nd 0.97 h (treatment B) after drug administration The corresponding va lues for the infusion were 339.6 ng/ml and 2.59 h in the mean. For the areas under the cur ve (AUC(0-infinity)) mean values of 2733 (treatme nt A), 2724 (treatment B) and 2877 h x ng/ml (treatmetzt C) were found . The absolute bioavailability of both oral treatments revealed values of 95.00% and 94.74% for treatments A and B, respectively. The statis tical comparison (ANOVA, confidence intervals) of the pharmacokinetic parameters showed bioequivalence between both oral preparations and eq uivalence in the amount of drug absorption between both oral formulati ons and the i.v.-infusion. The observed undesired side effects (e.g. h eadache or nausea) are well known to occur after IS-5-MN administratio n.