Mechanism of absorption enhancement in humans after rectal administration of ampicillin in suppositories containing sodium caprate

Purpose. The medium chain fatty acid sodium caprate (C10) is approved as an absorption enhancer but its mechanism of action has not been studied in humans. The aim of this study was to investigate the mechanism of action of C10 in human subjects after rectal administration. Methods, Twelve healthy human subjects were randomised to receive ampicillin suppositories with (ARI-CIO) or without (AM) CIO, Serum and urine samples were collected and analysed for ampicillin by HPLC. Rectal biopsies were taken before and 25 min (approximate time of maximum serum concentration, C-max, for ampicillin) and 185 min (during the final part of the elimination phase) after rectal administration of the suppositories. The osmolality of the rectal fluid was also measured. Results, AM-CIO administration increased C-max, area under the serum concentration-time curve (AUG) and urinary recovery of ampicillin 2.6-, 2.3- and 1.8-fold, respectively, compared to AM. Histological examination of the biopsies showed that AM-CIO exposure resulted in reversible mucosal damage that occurred at the same time as the C-max for ampicillin while AM prolonged mucosal damage. A reversible increase in rectal fluid osmolality was observed with both treatments. Conclusions. AM-C10-enhanced absorption of ampicillin coincides with non-specific damage to the rectal mucosa. CIO itself as well as the suppository base and the hyperosmolality of the rectal fluid contributed to this effect. However, the histological damage was reversible with AM-C10, suggesting that CIO also has a protective effect on the rectal mucosa.