Hu M, Subramanian P, Mosberg H I, Amidon G L
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Pharm Res. 1989 Jan;6(1):66-70. doi: 10.1023/a:1015855820488.
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 from 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.
采用原位肠灌注法研究了L-α-甲基多巴（I）的五种二肽基衍生物的肠道通透性。与L-α-甲基多巴相比，这些二肽的通透性显著增加。增加幅度为4至20倍。这些结果表明，肽转运系统在结构上比氨基酸转运系统特异性更低，可作为肽类似物的吸收途径。二肽L-α-甲基多巴-L-苯丙氨酸相对于氨基酸类似物L-α-甲基多巴所表现出的动力学优势表明，肽载体可能是改善药理活性氨基酸类似物肠道吸收的一条途径。此外，所选二肽基衍生物的体外水解研究初步结果表明，肽载体系统可作为前药策略的基础。
