PASSIVE AND CARRIER-MEDIATED INTESTINAL-ABSORPTION COMPONENTS OF CAPTOPRIL
PASSIVE AND CARRIER-MEDIATED INTESTINAL-ABSORPTION COMPONENTS OF CAPTOPRIL
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DOI：
10.1002/jps.2600771204
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发表时间：
1988-12-01
影响因子：
3.8
通讯作者：
AMIDON, GL
中科院分区：
文献类型：
--
作者：
HU, M;AMIDON, GL
采用单次灌流法研究卡托普利在禁食大鼠的肠道吸收机制。采用高效液相色谱法测定卡托普利和卡托普利二硫的含量。采用改良的边界层溶液测定肠壁的表观通透性(PW*)。结果表明，卡托普利在小肠中具有很强的渗透性，在结肠中不具有渗透性，在小肠中的渗透性与pH和浓度有关。载体的估计参数为：Km*6 mm；Jmax*，12 mm；Pc*2。卡托普利在小肠中也有显著的被动吸收成分。再加入85 mM甘氨酸(2.5倍)、15 mM甘氨酸(4倍)、二肽混合物(4.5倍)、0.5 mM 2，4-二硝基苯酚(4倍)和10 mM头孢拉定(6倍)，均能显著降低卡托普利的肠通透性。这是首次证明血管紧张素转换酶(ACE)抑制剂至少部分是通过载体介导的过程通过多肽载体系统在肠道中转运的。此外，结果表明，该多肽载体系统可以运输底物而不需要“N”端的氮原子。
The intestinal absorption mechanism of captopril was investigated in fasted rats using a single-pass perfusion method. Captopril and captopril disulfide were analyzed by HPLC. A modified boundary-layer solution was applied to determine the apparent intestinal wall permeabilities (Pw*). The results indicated that captopril is very permeable in the small intestine but not in the colon, and the permeability in the small intestine is both pH and concentration dependent. The estimated parameters for the carrier are:Km*6 mM;Jmax*, 12 mM; andPc*2. There is also a significant passive component to captopril absorption in the small intestine. Furthermore, the intestinal permeability of captopril was significantly decreased by the withdrawal of sodium from the perfusate (3 times), and the addition of 85 mM of gly-gly (2.5 times), 15 mM of gly-pro (4 times), dipeptide mixture (4.5 times), 0.5 mM of 2,4-dinitrophenol (4 times), and 10 mM of cephradine (6 times). This is the first demonstration that an angiotensin converting enzyme (ACE) inhibitor is at least in part transported by a carrier-mediated process in the intestine via the peptide carrier system. In addition, the results showed that the peptide carrier system can transport a substrate without a “N” terminal nitrogen atom.