van Hoogdalem E J, Heijligers-Feijen C D, de Boer A G, Verhoef J C, Breimer D D
Division of Pharmacology, Sylvius Laboratories, Leiden University, The Netherlands.
Pharm Res. 1989 Jan;6(1):91-5. doi: 10.1023/a:1015864022305.
The stability of the neuroleptic peptide des-enkephalin-gamma-endorphin (DE gamma E; Org 5878) in the rectal lumen and the rectal bioavailability of DE gamma E were investigated in conscious rats. Furthermore, the influence of peptidase inhibition, peptidase saturation, and absorption enhancement on DE gamma E bioavailability were evaluated. Na2EDTA (0.25%, w/v) prolonged the degradation half-life of DE gamma E in the ligated colon from 33 +/- 7 to 93 +/- 45 min. Without adjuvant, tritium-labeled DE gamma E was absorbed from the rat rectum to a very low extent (0-4%). After administration of an excess of unlabeled DE gamma E or with Na2EDTA, comparable results were obtained. The medium-chain glyceride preparation MGK markedly enhanced the rectal DE gamma E bioavailability, up to 8-20%, which was further increased to 10-44% by coadministration of Na2EDTA. No substantial influence of varying the rectal delivery rate was observed. The results suggest that absorption enhancement and enzyme inhibition both are essential for effective increase of rectal peptide bioavailability.
在清醒大鼠中研究了抗精神病肽去甲脑啡肽-γ-内啡肽（DEγE；Org 5878）在直肠腔中的稳定性以及DEγE的直肠生物利用度。此外，评估了肽酶抑制、肽酶饱和以及吸收增强对DEγE生物利用度的影响。Na2EDTA（0.25%，w/v）将结扎结肠中DEγE的降解半衰期从33±7分钟延长至93±45分钟。在无佐剂的情况下，氚标记的DEγE从大鼠直肠的吸收程度非常低（0 - 4%）。给予过量未标记的DEγE或与Na2EDTA共同给药时，得到了类似的结果。中链甘油酯制剂MGK显著提高了直肠DEγE的生物利用度，可达8 - 20%，通过与Na2EDTA共同给药进一步提高至10 - 44%。未观察到改变直肠给药速率有实质性影响。结果表明，吸收增强和酶抑制对于有效提高直肠肽生物利用度均至关重要。
