Gould Sarah, Scott Robert C
Safety Assessment, AstraZeneca UK Limited, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.
Food Chem Toxicol. 2005 Oct;43(10):1451-9. doi: 10.1016/j.fct.2005.03.007. Epub 2005 Apr 19.
2-Hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) is an alternative to alpha-, beta- and gamma-cyclodextrin, with improved water solubility and may be more toxicologically benign. This paper reviews the toxicity of HP-beta-CD, using both literature information and novel data, and presents new information. In addition, it includes a brief review from studies of the metabolism and pharmacokinetics of HP-beta-CD in both humans and animals. This review concludes that HP-beta-CD is well tolerated in the animal species tested (rats, mice and dogs), particularly when dosed orally, and shows only limited toxicity. In short duration studies, there were slight biochemical changes whereas studies of a longer duration, up to three months, produced additional minor haematological changes but no histopathological changes. When dosed intravenously, histopathological changes were seen in the lungs, liver and kidney but all findings were reversible and no effect levels were achieved. The carcinogenicity studies showed an increase in tumours in rats in the pancreas and intestines which are both considered to be rat-specific. There were also non-carcinogenic changes noted in the urinary tract, but these changes were also reversible and did not impair renal function. There were no effects on embryo-foetal development in either rats or rabbits. HP-beta-CD has been shown to be well tolerated in humans, with the main adverse event being diarrhoea and there have been no adverse events on kidney function, documented to date.
2-羟丙基-β-环糊精（HP-β-CD）是α-、β-和γ-环糊精的替代物，具有更好的水溶性，且在毒理学上可能更安全。本文利用文献信息和新数据对HP-β-CD的毒性进行了综述，并呈现了新的信息。此外，还简要回顾了HP-β-CD在人和动物体内的代谢及药代动力学研究。该综述得出结论，HP-β-CD在所测试的动物物种（大鼠、小鼠和犬）中耐受性良好，尤其是经口服给药时，仅表现出有限的毒性。在短期研究中，出现了轻微的生化变化，而在长达三个月的长期研究中，除了轻微的血液学变化外未产生组织病理学变化。静脉给药时，在肺、肝和肾中观察到组织病理学变化，但所有发现都是可逆的，且未达到无效应水平。致癌性研究表明，大鼠胰腺和肠道出现肿瘤增加，这些都被认为是大鼠特有的。在尿路中也发现了非致癌性变化，但这些变化也是可逆的，且未损害肾功能。在大鼠或兔中，对胚胎-胎儿发育均无影响。HP-β-CD已被证明在人体中耐受性良好，主要不良事件为腹泻，且迄今为止未记录到对肾功能的不良事件。
