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 stu died in humans. The aim of this study was to investigate the mechanism of action of C10 in human subjects after rectal administration. Metho ds, Twelve healthy human subjects were randomised to receive ampicilli n suppositories with (ARI-CIO) or without (AM) CIO, Serum and urine sa mples were collected and analysed for ampicillin by HPLC. Rectal biops ies were taken before and 25 min (approximate time of maximum serum co ncentration, C-max, for ampicillin) and 185 min (during the final part of the elimination phase) after rectal administration of the supposit ories. The osmolality of the rectal fluid was also measured. Results, AM-CIO administration increased C-max, area under the serum concentrat ion-time curve (AUG) and urinary recovery of ampicillin 2.6-, 2.3- and 1.8-fold, respectively, compared to AM. Histological examination of t he biopsies showed that AM-CIO exposure resulted in reversible mucosal damage that occurred at the same time as the C-max for ampicillin whi le AM prolonged mucosal damage. A reversible increase in rectal fluid osmolality was observed with both treatments. Conclusions. AM-C10-enha nced absorption of ampicillin coincides with non-specific damage to th e rectal mucosa. CIO itself as well as the suppository base and the hy perosmolality of the rectal fluid contributed to this effect. However, the histological damage was reversible with AM-C10, suggesting that C IO also has a protective effect on the rectal mucosa.