CAJ | 학술논문

青蒿素及其衍生物是目前广泛应用的一线抗疟药，能杀灭多种寄生虫如疟原虫、血吸虫、弓形虫、利什曼原虫等，还能调节免疫用于治疗红斑狼疮和类风湿性关节炎，体外细胞实验证实对多种人源性肿瘤细胞具有明显杀伤作用。研究发现，此类化合物的结构中存在内过氧桥，催化断裂后产生的碳中心自由基和活性氧，是其发挥药理学和毒理学作用的结构基础。临床上大量的抗疟治疗迄今未见明显的严重不良反应，具有很高的安全性，而动物急性毒性和慢性毒性实验等临床前研究发现药物的高剂量或长期暴露能导致多个系统和器官的毒性效应。本文对青蒿素及其衍生物的神经毒性、胚胎毒性、遗传毒性、造血和免疫毒性、心脏毒性等，从体外细胞水平、整体动物水平和人体临床试验，以及药物代谢动力学研究新进展等方面进行综述，以总结青蒿素类药物毒理学研究的热点和方向，为以扩大青蒿素类药物临床适应证，选择安全的给药途径、剂量和检测指标为目的的毒理学评价和研究提供支持，更好地服务临床。
청호소급기연생물시목전엄범응용적일선항학약，능살멸다충기생충여학원충、혈흡충、궁형충、리십만원충등，환능조절면역용우치료홍반랑창화류풍습성관절염，체외세포실험증실대다충인원성종류세포구유명현살상작용。연구발현，차류화합물적결구중존재내과양교，최화단렬후산생적탄중심자유기화활성양，시기발휘약이학화독이학작용적결구기출。림상상대량적항학치료흘금미견명현적엄중불량반응，구유흔고적안전성，이동물급성독성화만성독성실험등림상전연구발현약물적고제량혹장기폭로능도치다개계통화기관적독성효응。본문대청호소급기연생물적신경독성、배태독성、유전독성、조혈화면역독성、심장독성등，종체외세포수평、정체동물수평화인체림상시험，이급약물대사동역학연구신진전등방면진행종술，이총결청호소류약물독이학연구적열점화방향，위이확대청호소류약물림상괄응증，선택안전적급약도경、제량화검측지표위목적적독이학평개화연구제공지지，경호지복무림상。
One of the most promising antimalarial drugs which are widely used throughout the world is the artemisinin (ARS)and its derivatives,e.g.,artemether,arteether,and artesunate.Their true potential lies in broader anti-disease applications.The mechanism of action of these compounds appears to involve the endoperoxide bridge to produce carbon-centred free radicals.Large clinical studies did not show serious side effects,however,there is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity.Therefore,a final and definitive statement on the safety of artemisinins still cannot be made.In contrast,animal experiments at high doses shown considerable toxicity upon application of artemisinins.In the present review,the authors give a comprehensive overview on toxicity studies in cell culture and in animals (mice,rats,rabbits,dogs,and monkeys)as well as on toxicity reported in human clinical trials.The authors emphasize the current knowledge on neurotoxicity,embryotoxicity, genotoxicity,hemato-and immunotoxicity and cardiotoxicity.Rapid elimination of artemisinins after oral intake represents a relatively safe route of administration compared to delayed drug release after intra-muscular (im ) injection. There are drug-related differences, i.e., intramuscular application of artemether or arteether,but not to artesunate,which is safe and gives good profiles after im administra-tion in severe malaria.It might also be important in determining dose limitations for treatment of other diseases such as cancer.Questions about dosing regimens,safety of long-term use and possible inter-actions with existing therapies and toxicities that might be related to the treatment of tumors should be answered by appropriate clinical and preclinical studies.