caa a22 4500 477126472 CHVBK 20180405111651.0 cr unu---uuuuu 170330e19970701xx s 000 0 eng 10.1023/A:1012112219578 doi (NATIONALLICENCE)springer-10.1023/A:1012112219578 Mechanism of Absorption Enhancement in Humans After Rectal Administration of Ampicillin in Suppositories Containing Sodium Caprate [Elektronische Daten] [Tuulikki Lindmark, Johan Söderholm, Gunnar Olaison, Gunnar Alván, Göran Ocklind, Per Artursson] 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 (AM-C10) or without (AM) C10. 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, Cmax, 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-C10 administration increased Cmax, area under the serum concentration-time curve (AUC) 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-C10 exposure resulted in reversible mucosal damage that occurred at the same time as the Cmax for ampicillin while AM prolonged mucosal damage. A reversible increase in rectal fluid osmolality was observed with both treatments. Conclusions. AM-ClO-enhanced absorption of ampicillin coincides with non-specific damage to the rectal mucosa. C10 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 C10 also has a protective effect on the rectal mucosa. Plenum Publishing Corporation, 1997 absorption enhancement nationallicence medium chain fatty acid nationallicence sodium caprate nationallicence rectal drug absorption nationallicence tight junction nationallicence suppository nationallicence epithelial permeability nationallicence human rectal morphology nationallicence Lindmark Tuulikki Dept. of Pharmacy, Uppsala University, S-75123, Uppsala, Sweden aut Söderholm Johan Dept. of Surgery, University Hospital, S-58185, Linköping, Sweden aut Olaison Gunnar Dept. of Surgery, University Hospital, S-58185, Linköping, Sweden aut Alván Gunnar Dept. of Clinical Pharmacology, Huddinge Hospital, S-141 68, Huddinge, Sweden aut Ocklind Göran Dept. of Pharmacy, Uppsala University, S-75123, Uppsala, Sweden aut Artursson Per Dept. of Pharmacy, Uppsala University, S-75123, Uppsala, Sweden aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 930-935 0724-8741 14:7<930 1997 14 11095 https://doi.org/10.1023/A:1012112219578 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012112219578 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lindmark Tuulikki Dept. of Pharmacy, Uppsala University, S-75123, Uppsala, Sweden aut NATIONALLICENCE 700 1- Söderholm Johan Dept. of Surgery, University Hospital, S-58185, Linköping, Sweden aut NATIONALLICENCE 700 1- Olaison Gunnar Dept. of Surgery, University Hospital, S-58185, Linköping, Sweden aut NATIONALLICENCE 700 1- Alván Gunnar Dept. of Clinical Pharmacology, Huddinge Hospital, S-141 68, Huddinge, Sweden aut NATIONALLICENCE 700 1- Ocklind Göran Dept. of Pharmacy, Uppsala University, S-75123, Uppsala, Sweden aut NATIONALLICENCE 700 1- Artursson Per Dept. of Pharmacy, Uppsala University, S-75123, Uppsala, Sweden aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 930-935 0724-8741 14:7<930 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer