USE OF THE PEPTIDE CARRIER SYSTEM TO IMPROVE THE INTESTINAL-ABSORPTION OF L-ALPHA-METHYLDOPA - CARRIER KINETICS, INTESTINAL PERMEABILITIES, AND INVITRO HYDROLYSIS OF DIPEPTIDYL DERIVATIVES OF L-ALPHA-METHYLDOPA
USE OF THE PEPTIDE CARRIER SYSTEM TO IMPROVE THE INTESTINAL-ABSORPTION OF L-ALPHA-METHYLDOPA - CARRIER KINETICS, INTESTINAL PERMEABILITIES, AND INVITRO HYDROLYSIS OF DIPEPTIDYL DERIVATIVES OF L-ALPHA-METHYLDOPA
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DOI：
10.1023/a:1015855820488
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发表时间：
1989-01-01
影响因子：
3.7
通讯作者：
AMIDON, GL
中科院分区：
文献类型：
--
作者：
HU, M;SUBRAMANIAN, P;AMIDON, GL
L-α-的五种二肽基衍生物的肠道渗透性甲基多巴（I）的肠灌流实验。与L-α-二肽相比，二肽显示出其渗透性的显著增加。甲基多巴增加了4至20倍。这些结果表明，肽转运系统的结构特异性低于氨基酸转运系统，可用作肽类似物的吸收途径。二肽L-α-甲基多巴-L-苯丙氨酸，超过氨基酸类似物L-α-甲基多巴，表明肽载体将是一种可能的途径，以改善肠道吸收的活性氨基酸类似物。此外，所选二肽基衍生物的体外水解研究的初步结果表明，肽载体系统可用作前药策略的基础。
Intestinal permeabilities of five dipeptidyl derivatives of L-.alpha.-methyldopa (I) were studied by an in situ intestinal perfusion method. The dipeptides displayed a significant increase in their permeabilities compared to L-.alpha.-methyldopa. The increases ranged form 4 to 20 times. These results suggest that the peptide transport system is less structurally specific than the amino acid transport systems and can be used as an absorption pathway for peptide analogues. The kinetic advantage demonstrated by the dipeptide, L-.alpha.-methyldopa-L-phenylalanine, over the amino acid analogue, L-.alpha.-methyldopa, suggests that the peptide carrier would be a possible route for improving the intestinal absorption of pharmacologically active amino acid analogues. Furthermore, the preliminary results of in vitro hydrolysis studies of selected dipeptidyl derivatives indicate that the peptide carrier system could be used as a base for a prodrug strategy.