The intestinal uptake of "enzymatically-stable" peptide drugs in rats as influenced by D-glucose in situ.
The intestinal uptake of "enzymatically-stable" peptide drugs in rats as influenced by D-glucose in situ.
复制标题
大鼠肠道对“酶稳定”肽药物的摄取受原位 D-葡萄糖的影响。
DOI：
10.1016/0024-3205(94)90132-5
复制
发表时间：
1994
期刊：
影响因子：
6.1
通讯作者：
Fleisher,D
中科院分区：
文献类型：
--
作者：
Hu,Z;Tse,EG;Monkhouse,DC;Oh,CK;Fleisher,D
在先前的原位和在体灌注研究中，几种低分子量药物的肠吸收通过管腔D-葡萄糖的存在而增加。本研究的目的是确定这种进食状态效应改善渗透性差的小肽和肽样药物的肠道摄取的潜力。采用原位单向灌流技术，测定了D-京托啡肽（D-kyotorphin）、头孢拉定（Cefradine）、生长激素释放肽（GHRP-6）和生长抑素类似物奥曲肽（Octreotide）的空肠壁通透性（Pw）及相应的净水通量。葡萄糖显示出增强较小的（二-和三-）肽的摄取，但不是较大的肽，尽管事实上，葡萄糖引起了显着的净水吸收与四种肽药物。结论是葡萄糖通过溶剂阻力增强小肽的空肠渗透性，并且这种增强作用受肽分子大小的限制。对不可代谢的3-O-甲基葡萄糖的研究表明，葡萄糖引起的跨粘膜质子梯度的增加有助于在较小肽中观察到的载体介导的转运。
In previousin situandin vivorat perfusion studies, the intestinal absorption of several low molecular weight drugs was increased by the presence of luminal D-glucose. The intent of this study was to determine the potential of this fed-state effect to improve the intestinal uptake of poorly permeable, small peptide and peptide-like drugs. Jejunal wall permeabilities (Pw∗) of di-(D-kyotorphin), tri-(cephradine), hexa-(growth hormone releasing peptide, GHRP-6) and octa-(octreotide, a somatostatin analogue) peptides and corresponding net water fluxes were determined in rats using anin situsingle-pass perfusion technique. Glucose was shown to enhance the uptake of the smaller (di-and tri-) peptides but not the larger peptides despite the fact that glucose elicited a significant net water absorption with each of the four peptide drugs. It is concluded that glucose enhances jejunal permeabilities of smaller peptides by solvent drag and the enhancement is limitedin situby peptide molecular size. The studies with nonmetabolizable 3-O-methylglucose suggest that the augmentation of the proton gradient across the transmucosal membrane by glucose contributes to the carrier-mediated transport observed with the smaller peptides.