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.

译文

:在清醒的大鼠中研究了抗精神病药肽去脑啡肽-γ-内啡肽(DE gamma E; Org 5878)在直肠腔中的稳定性以及DE gamma E的直肠生物利用度。此外,评估了肽酶抑制,肽酶饱和度和吸收增强对DEγE生物利用度的影响。 Na2EDTA(0.25%,w / v)将DEγE在结扎结肠中的降解半衰期从33 /-7延长至93 /-45分钟。在没有佐剂的情况下,DE标记的DEγE从大鼠直肠的吸收程度非常低(0-4%)。施用过量的未标记DEγE或与Na2EDTA一起使用后,可获得可比的结果。中链甘油酯制剂MGK显着提高了直肠DEγE的生物利用度,高达8-20%,通过与Na2EDTA并用,进一步提高了10-44%。没有观察到改变直肠分娩率的实质性影响。结果表明吸收增强和酶抑制两者对于有效增加直肠肽的生物利用度都是必不可少的。

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