Mummaneni V, Dressman J B
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Pharm Res. 1994 Nov;11(11):1599-604. doi: 10.1023/a:1018961805118.
The H2-receptor antagonists exhibit unusual absorption behavior in that double peaks often occur after oral administration. Moreover, administration with some high potency antacids decreases the extent of absorption. To date, no explanation that can completely account for these observations has been advanced. One problem is that there is a lack of consensus as to the mechanism of absorption of the H2-receptor antagonists from the gastrointestinal tract. In the studies reported here, the mechanism and regional dependence of intestinal uptake of two H2-receptor antagonists, cimetidine and ranitidine, were investigated in rats using the in vitro everted ring technique. The uptake rate of cimetidine from both jejunum and colon was linear with concentration (in the range of 0.0005-40 mM), and there was no significant competition for uptake in the presence of the structurally similar H2-receptor antagonists, famotidine and ranitidine. In the case of ranitidine too, the uptake rate from the jejunum and colon was linear with concentration (in the range of 0.0005-5 mM), and there was no competition for uptake by either famotidine or cimetidine. These data indicate that uptake of cimetidine and ranitidine in the rat jejunum and colon occurs by a predominantly passive process. Both cimetidine and ranitidine exhibited regional differences in uptake rate. Uptake tended to be greatest in the ileum, similar in duodenum and jejunum, and lowest in the colon. However, differences in uptake rates between locations in the small intestine appeared to be too modest to account for the double peak behavior of either compound.
H2受体拮抗剂呈现出异常的吸收行为，口服给药后常出现双峰现象。此外，与某些高效抗酸剂合用会降低吸收程度。迄今为止，尚未提出能完全解释这些现象的原因。一个问题是，关于H2受体拮抗剂从胃肠道吸收的机制尚无共识。在本文报道的研究中，采用体外外翻肠环技术，在大鼠体内研究了两种H2受体拮抗剂西咪替丁和雷尼替丁的肠道摄取机制及区域依赖性。西咪替丁在空肠和结肠的摄取速率与浓度呈线性关系（浓度范围为0.0005 - 40 mM），在结构相似的H2受体拮抗剂法莫替丁和雷尼替丁存在的情况下，摄取没有明显竞争。雷尼替丁的情况也是如此，其在空肠和结肠的摄取速率与浓度呈线性关系（浓度范围为0.0005 - 5 mM），法莫替丁或西咪替丁对其摄取均无竞争。这些数据表明，大鼠空肠和结肠中，西咪替丁和雷尼替丁的摄取主要通过被动过程进行。西咪替丁和雷尼替丁在摄取速率上均表现出区域差异。回肠的摄取往往最大，十二指肠和空肠相似，结肠最低。然而，小肠不同部位之间的摄取速率差异似乎过小，无法解释这两种化合物的双峰行为。
