Tsukamoto Ikuko, Hossain Akram, Yamaguchi Fuminori, Hirata Yuko, Dong Youyi, Kamitori Kazuyo, Sui Li, Nonaka Machiko, Ueno Masaki, Nishimoto Kazuyuki, Suda Hirofumi, Morimoto Kenji, Shimonishi Tsuyoshi, Saito Madoka, Song Tao, Konishi Ryoji, Tokuda Masaaki
Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan.
Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan ; Matsutani Chemical Industry Co, Ltd, Itami, Japan.
Drug Des Devel Ther. 2014 Oct 17;8:1955-64. doi: 10.2147/DDDT.S60247. eCollection 2014.
The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia.
This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of (14)C-labeled D-psicose or glucose intravenously to C3H mice.
Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 μg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of (14)C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain.
D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal study, it is necessary to implement human trials to study the metabolism pathway, which would give an important guide for human intake and food application of D-psicose.
本研究旨在评估稀有糖D-阿洛酮糖的肠道吸收、器官分布及尿排泄情况。D-阿洛酮糖是D-果糖的一种三碳立体异构体，目前正处于研究阶段，已发现其对高血糖和高血脂具有显著疗效。
本研究使用通过酶法由放射性D-阿洛糖合成的放射性D-阿洛酮糖进行。在给Wistar大鼠口服和静脉注射后不同时间点直至2小时，以及单次口服给药（100mg/kg体重）7天后，测量全血、尿液和器官中的浓度。还通过向C3H小鼠静脉注射100mg/kg体重的（14）C标记的D-阿洛酮糖或葡萄糖进行放射自显影。
口服给药后，D-阿洛酮糖很容易进入血液。1小时时观察到最大血药浓度（48.5±15.6μg/g）。1小时内尿排泄率为20%，2小时内为33%。仅在肝脏中检测到器官蓄积。静脉注射后，血药浓度下降，半衰期为57分钟，1小时内尿排泄率高达近50%。与口服给药结果类似，仅在肝脏中检测到器官蓄积。单次口服给药7天后，全身剩余量小于1%。小鼠的放射自显影结果与大鼠相似。在肝脏、肾脏和膀胱中观察到（14）C标记的D-阿洛酮糖的高信号。有趣的是，在脑中未观察到D-阿洛酮糖的蓄积。
D-阿洛酮糖口服后吸收良好，口服和静脉注射后均迅速消除，作用持续时间短。该研究为D-阿洛酮糖的进一步药物开发提供了有价值的药代动力学数据。由于研究结果主要基于动物研究，有必要开展人体试验以研究其代谢途径，这将为D-阿洛酮糖的人体摄入和食品应用提供重要指导。
