Tsuji A, Miyamoto E, Terasaki T, Yamana T
J Pharm Sci. 1982 Apr;71(4):403-6. doi: 10.1002/jps.2600710407.
The intestinal absorption of alpha-esters of carbenicillin disodium, carbenicillin phenyl sodium, and carbenicillin indanyl sodium was investigated using the in situ rat intestinal recirculating method. In the in situ intestinal lumen at pH 7, two prodrugs were rapidly converted to poorly absorbable carbenicillin, possibly by the action of intestinal nonspecific esterase in competition with the slow absorption of prodrugs. At pH 5, the reduced action of esterase and the increased absorption rate after 3 hr resulted in 50 and 60% absorption of carbenicillin phenyl sodium and carbenicillin indanyl sodium, respectively. The absorption rate constants determined for both prodrugs were in good agreement with the prediction from the quantitative structure-absorption rate relationship derived from the two-compartment aqueous diffusion model.
采用大鼠原位肠循环法研究了羧苄西林二钠α酯、羧苄西林苯酯钠和羧苄西林茚满酯钠的肠道吸收情况。在pH 7的原位肠腔中，两种前体药物迅速转化为吸收性差的羧苄西林，这可能是由于肠道非特异性酯酶的作用，与前体药物缓慢吸收形成竞争。在pH 5时，酯酶活性降低以及3小时后吸收速率增加，导致羧苄西林苯酯钠和羧苄西林茚满酯钠的吸收率分别达到50%和60%。两种前体药物的吸收速率常数与从双室水扩散模型推导的定量结构-吸收速率关系预测结果高度一致。
