Absorption of Isosorbide-5-Nitrate from the Gastrointestinal Tract

Summary

The absorption of the antianginal drug isosorbide-5-nitrate (IS-5-N) from different regions of the gastrointestinal tract was investigated in nine male human subjects using the High Frequency-capsule (HF-capsule) technique. The HF-capsule, loaded with 20 mg IS-5-N, was opened in the stomach, duodenum, middle jejunum, and colon ascendens of two subjects each, and in the upper jejunum of another subject.

Residence times of the capsule in the gastrointestinal tract from ingestion until opening ranged from 1.1 to 2.3 hours. The absorption of IS-5-N was estimated on the basis of its plasma concentrations. Areas under the curve, peak times and peak heights proved to be not dependent on the gastrointestinal site of absorption. In most cases the absorption was completed within 30–40 min after opening of the HF-capsule.

The results suggest to reject the assumption of a local absorption window above the colon transversum. These findings could be successfully applied to the rational design of a sustained release formulation of IS-5-N.