De Bie A T, Van Ommen B, Bär A
TNO-Nutrition and Food Research Institute, Zeist, 3700 AJ, The Netherlands.
Regul Toxicol Pharmacol. 1998 Apr;27(2):150-8. doi: 10.1006/rtph.1998.1219.
The absorption, disposition, metabolism, and excretion of 14C-labeled gamma-cyclodextrin ([14C]gamma-CD) was examined in four separate experiments with Wistar rats. In experiment 1, [14C]gamma-CD (25 microCi, 600 mg/kg body wt) was administered intravenously to four male and four female conventional rats. In experiment 2, [14C]gamma-CD (25 microCi, 1000 mg/kg body wt) was given by gavage to four male and four female germ-free rats. In experiments 3 and 4, [14C]gamma-CD (25 and 100 microCi, respectively, 1000 mg/kg body wt) was given to four male and four female conventional rats by gavage. In all experiments, 14C was measured in respiratory CO2, urine, feces, contents of the gastrointestinal tract, blood, main organs, and residual carcass. The chemical identity of the 14C-labeled compounds was examined by HPLC in urine (experiments 1-4), blood (experiments 1 and 4), and samples of intestinal contents (experiments 3 and 4). Recovered 14C was expressed as a percentage of the administered dose. Total recovery of 14C varied between about 90% (experiments 3 and 4) and 100% (experiments 1 and 2). Experiment 1 showed that about 90% of intravenously administered gamma-CD is excreted in urine within 24 h. During the first 2 h after dosing, plasma 14C levels decreased rapidly (t1/2, 15-20 min). The remaining 10% of the dose was probably excreted into the gastrointestinal tract with bile and saliva. In addition, some [14C]gamma-CD may have been degraded by plasma and tissue amylases. Since glucose is the common product of systemic hydrolysis and intestinal digestion, it is not possible to quantitate the relative flux of [14C]gamma-CD through these two pathways. Upon oral administration of [14C]gamma-CD to germ-free rats (experiment 2), about 66% of the label was expired as CO2 within 24 h. The rate of 14C exhalation reached a maximum at 90 min after dosing and then declined steadily. In the urine, and in the contents of the cecum and colon collected at 24 h, [14C]gamma-CD was not found (except for a trace in the cecum of females). In conventional rats (experiments 3 and 4), a similar, fast appearance of respiratory 14CO2 was observed. There was no delayed formation of 14CO2 due to incomplete digestion and subsequent microbial fermentation in the cecum and colon. In pooled urine collected at 4 h after dosing, a small amount of unchanged [14C]gamma-CD was detected (experiment 4). From this result, it was estimated that less than 0.02% of ingested intact gamma-CD was absorbed and excreted with the urine. It is concluded from the data that ingested [14C]gamma-CD is rapidly and essentially completely digested in the small intestine to absorbable [14C]glucose. The absorption of intact [14C]gamma-CD by passive diffusion is very low (<0.02%). Therefore, the metabolism of gamma-CD resembles closely that of starch or linear dextrins.
在四项分别以Wistar大鼠进行的实验中，研究了14C标记的γ-环糊精（[14C]γ-CD）的吸收、分布、代谢及排泄情况。实验1中，给4只雄性和4只雌性普通大鼠静脉注射[14C]γ-CD（25微居里，600毫克/千克体重）。实验2中，给4只雄性和4只雌性无菌大鼠灌胃[14C]γ-CD（25微居里，1000毫克/千克体重）。实验3和4中，分别给4只雄性和4只雌性普通大鼠灌胃[14C]γ-CD（分别为25和100微居里，1000毫克/千克体重）。在所有实验中，测定了呼吸二氧化碳、尿液、粪便、胃肠道内容物、血液、主要器官及残留 carcass 中的14C。通过高效液相色谱法检测了尿液（实验1 - 4）、血液（实验1和4）及肠道内容物样本（实验3和4）中14C标记化合物的化学特性。回收的14C以给药剂量的百分比表示。14C的总回收率在约90%（实验3和4）至100%（实验1和2）之间变化。实验1表明，静脉注射的γ-CD约90%在24小时内随尿液排出。给药后的前2小时内，血浆14C水平迅速下降（半衰期，15 - 20分钟）。其余10%的剂量可能随胆汁和唾液排入胃肠道。此外，一些[14C]γ-CD可能已被血浆和组织淀粉酶降解。由于葡萄糖是全身水解和肠道消化的共同产物，因此无法定量[14C]γ-CD通过这两条途径的相对通量。给无菌大鼠口服[14C]γ-CD（实验2）后，约66%的标记物在24小时内以二氧化碳形式呼出。14C呼出率在给药后90分钟达到最大值，然后稳步下降。在尿液以及24小时收集的盲肠和结肠内容物中，未发现[14C]γ-CD（雌性盲肠中有微量除外）。在普通大鼠中（实验3和4），观察到呼吸14CO2有类似的快速出现情况。由于盲肠和结肠中消化不完全及随后的微生物发酵，未出现14CO2的延迟形成。给药后4小时收集的混合尿液中，检测到少量未变化的[14C]γ-CD（实验4）。根据该结果估计，摄入的完整γ-CD经尿液吸收和排泄的比例小于0.02%。从数据得出结论，摄入的[14C]γ-CD在小肠中迅速且基本完全消化为可吸收的[14C]葡萄糖。完整的[14C]γ-CD通过被动扩散的吸收非常低（<0.02%）。因此，γ-CD的代谢与淀粉或线性糊精的代谢非常相似。
