Eflornithine for the treatment of human African trypanosomiasis
Eflornithine for the treatment of human African trypanosomiasis
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DOI：
10.1007/s00436-002-0766-5
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发表时间：
2003-06-01
影响因子：
2
通讯作者：
Brun, R
中科院分区：
文献类型：
--
作者：
Burri, C;Brun, R
依氟鸟氨酸是过去50年来唯一登记用于治疗非洲锥虫病的新分子。它是一种主要用于美拉索前列醇耐药的布氏冈比亚锥虫病例的备用药物。治疗冈比亚弓形虫昏睡病最常用的剂量方案是以100 mg kg(-1)体重为间隔，间隔6h，连续14天(儿童为150 mg kg(-1)体重)，短期输注依氟鸟氨酸。它对布氏锥虫的疗效有限，因为这种寄生虫天生缺乏敏感性，这种寄生虫基于较高的鸟氨酸脱羧酶转换率。依氟鸟氨酸治疗期间的药物不良反应频繁，其特点与其他治疗癌症的细胞毒药物相似。它们的发生和强度随着治疗时间的延长和患者一般情况的严重程度而增加。一般来说..。依氟鸟氨酸的不良反应在治疗结束后是可逆的。它们包括抽搐(7%)、恶心、呕吐和腹泻等胃肠道症状(10%-39%)、导致贫血、白细胞减少和血小板减少的骨髓毒性(25%-50%)、听力障碍(癌症患者为5%)和脱发(5%-10%)。这种药物可以阻止小鼠、大鼠和兔子的胚胎发育，但排泄到母乳中的程度尚不清楚。平均半衰期为3~4h，分布体积为0.351 kg(-1)。肾清除约2mlmin kg(-1)(静脉注射)并占扫毒工作的80%以上。口服10 mg kg(-1)剂量的生物利用度估计为54%。治疗成功的主要决定因素之一似乎是治疗过程中达到的脑脊液药物水平，研究表明，为了达到寄生虫的持续清除，必须达到L(-1)50毫摩尔以上的水平。基于其抗胰岛作用而不是杀锥虫的作用模式，它是一种相当缓慢的药物。
Eflornithine is the only new molecule registered for the treatment of human African trypanosomiasis over the last 50 years. It is the drug used mainly as a back-up for melarsoprol refractory Trypanosoma brucei gambiense cases. The most commonly used dosage regimen for the treatment of T. b. gambiense sleeping sickness consists of 100 mg kg(-1) body weight at intervals of 6 h for 14 days (150 mg kg(-1) body weight in children) of eflornithine given as short infusions. Its efficacy against Trypanosoma brucei rhodesiense is limited due to the innate lack of susceptibility of this parasite based on a higher ornithine decarboxylase turnover. Adverse drug reactions during eflornithine therapy are frequent and the characteristics are similar to other cytotoxic drugs for the treatment of cancer. Their occurrence and intensity increase with the duration of treatment and the severity of the general condition of the patient. Generally.. adverse reactions to eflornithine are reversible after the end of treatment. They include convulsions (7%), gastrointestinal symptoms like nausea, vomiting and diarrhea (10%-39%), bone marrow toxicity leading to anemia, leucopenia and thrombocytopenia (25-50%), hearing impairment (5% in cancer patients) and alopecia (5-10%). The drug arrests embryonic development in mice, rats and rabbits but the extent of excretion into breast milk is unknown. The mean half-life is around 3-4 h and the volume of distribution in the range of 0.35 1 kg(-1). Renal clearance is about 2 ml min kg(-1) (i.v.) and accounts for more than 80% of drug elimination. Bioavailability of an orally administered 10 mg kg(-1) dose was estimated at 54%. One of the major determinants of successful treatment seems to be the cerebrospinal fluid drug level reached during treatment, and it was shown that levels above 50 mumol l(-1) must be reached to attain the consistent clearance of parasites. Based on its trypanostatic rather than trypanocidal mode of action, it is a rather slow-acting drug.