Sund R B, Hillestad B
Acta Pharmacol Toxicol (Copenh). 1982 Oct;51(4):377-87. doi: 10.1111/j.1600-0773.1982.tb01040.x.
Phenolphthalein (PHEN), desacetylbisacodyl (DES) and oxyphenisatin (OXY) were incubated with everted sacs of the rat jejunum and stripped descending colon; the mucosal and serosal fluid were analysed with respect to free and conjugated diphenol by means of HPLC. Conjugates were measured as the amount of free diphenol in completely hydrolyzed samples less the amount before hydrolysis. A study with double-sided administration of PHEN revealed that diphenol uptake from and conjugate output to both sides followed a rectilinear course for 15-90 min. A standard incubation time of 60 min. was chosen for the subsequent experiments, in which the diphenols were administered at the mucosal side at a low and a high concentration. Diphenol uptake, i.e. the amount of free diphenol administered less the amount recovered at the mucosal side, varied in an order (PHEN greater than DES greater than OXY) which seems to be inversely related to the order of water solubility of the compounds. Tissue accumulation and conjugate output relative to uptake varied with the dose, and from one compound to another. At low initial concentration (20 nmol/ml), the compounds were transferred to the jejunal and colonic serosal fluid almost entirely as conjugates (greater than or equal to 95%); the transfer rates followed, qualitatively, the same order as above. In jejunum, more conjugates were released to the mucosal than to the serosal side; in colon the distribution was reversed. Increasing the dose to 100 nmol/ml caused a corresponding increase in uptake, but relative output decreased and tissue accumulation increased; thus demonstrating capacity limitation. With PHEN, the ratio of conjugated:free diphenol on the serosal side remained essentially unchanged; with DES in particular, but also with OXY the ratio decreased. These findings may be interpreted to mean that in case of PHEN capacity limitation is linked to conjugate efflux, while DES and OXY may be poor substrates for glucuronide formation as well. Experiments with serosal side administration like the double-sided PHEN experiments verified the dissimilar conjugate distribution in jejunal and colonic sacs; the phenomenon is to some extent discussed in the text. Identity tests gave evidence that the conjugates were mainly monoglucuronides.
将酚酞（PHEN）、去乙酰双醋酚丁（DES）和奥昔酚酞（OXY）与大鼠空肠和剥离的降结肠外翻肠囊一起孵育；通过高效液相色谱法分析黏膜和浆膜液中的游离和结合双酚。结合物的量通过完全水解样品中游离双酚的量减去水解前的量来测定。一项关于双侧给予PHEN的研究表明，在15 - 90分钟内，双侧的双酚摄取和结合物输出呈直线变化。后续实验选择60分钟的标准孵育时间，其中双酚以低浓度和高浓度在黏膜侧给药。双酚摄取，即给予的游离双酚量减去在黏膜侧回收的量，其变化顺序为（PHEN大于DES大于OXY），这似乎与化合物的水溶性顺序呈反比。相对于摄取的组织蓄积和结合物输出随剂量以及不同化合物而变化。在低初始浓度（20 nmol/ml）时，化合物几乎完全以结合物形式（大于或等于95%）转移到空肠和结肠浆膜液中；转移速率在定性上遵循上述相同顺序。在空肠中，释放到黏膜侧的结合物比释放到浆膜侧的多；在结肠中，分布情况相反。将剂量增加到100 nmol/ml会导致摄取相应增加，但相对输出减少且组织蓄积增加；从而证明存在容量限制。对于PHEN，浆膜侧结合型双酚与游离双酚的比例基本保持不变；特别是对于DES，以及OXY，该比例降低。这些发现可以解释为，对于PHEN，容量限制与结合物外排有关，而DES和OXY也可能是葡糖醛酸形成的不良底物。与双侧PHEN实验类似的浆膜侧给药实验证实了空肠和结肠肠囊中结合物分布的差异；文中在一定程度上讨论了该现象。同一性测试证明结合物主要是单葡糖醛酸酯。
