Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis
Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis
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DOI：
10.1056/nejm199912093412403
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发表时间：
1999-12-09
影响因子：
158.5
通讯作者：
Berman, J
中科院分区：
文献类型：
--
作者：
Jha, TK;Sundar, S;Berman, J
背景：目前尚无有效的口服药物治疗利什曼病感染。我们研究了可以口服的米替福辛治疗印度内脏利什曼病。米替福辛是一种影响细胞信号通路和膜合成的磷酸胆碱类似物。方法：这项研究是一项开放的、多中心的2期试验，其中4个30人队列每天服用50、100或150毫克的米替福辛，持续4或6周。120名患者，年龄从12岁到50岁不等，有食欲减退、发热和脾肿大，脾抽吸物中至少有中度(2+)利什曼病。寄生虫学治愈的定义是在治疗完成两周后，脾抽吸物中没有寄生虫。6个月后评估临床疗效。结果：所有120例患者均获初步寄生虫学治愈。6名患者有临床和寄生虫学复发；其余114名患者在治疗后6个月内未复发，治愈率为95%(95%可信区间，89%至98%)。每天服用米替福辛100毫克(约为每天每公斤体重2.5毫克)，连续四周，30名患者中有29名(97%)痊愈。胃肠道副作用常见(发生在62%的患者中)，但严重程度为轻至中度，没有患者因胃肠道副作用而停止治疗。在两名患者中，由于天冬氨酸转氨酶或肌酐水平升高而停止治疗；在这两名患者中，水平迅速恢复正常。12例患者治疗过程中天冬氨酸氨基转移酶升高至100~150U/L。结论：口服米替福辛是治疗印度内脏利什曼病的一种有效方法。(N Engl J Med 1999；341：1795-800)(C)1999年，马萨诸塞州医学会。
Background: There is no effective orally administered medication for any leishmania infection. We investigated miltefosine, which can be taken orally, for the treatment of Indian visceral leishmaniasis. Miltefosine is a phosphocholine analogue that affects cell-signaling pathways and membrane synthesis.Methods: The study was an open-label, multicenter, phase 2 trial in which four 30-person cohorts received 50, 100, or 150 mg of miltefosine per day for four or six weeks. The 120 patients, who ranged in age from 12 to 50 years, had anorexia, fever, and splenomegaly with at least moderate (2+) leishmania in a splenic aspirate. A parasitologic cure was defined by the absence of parasites in a splenic aspirate obtained two weeks after completion of treatment. The clinical response was assessed at six months.Results: In all 120 patients there was an initial parasitologic cure. Six patients had clinical and parasitologic relapses; the remaining 114 patients had not relapsed by six months after treatment, for a cure rate of 95 percent (95 percent confidence interval, 89 to 98 percent). With the regimen of 100 mg of miltefosine per day (approximately 2.5 mg per kilogram of body weight per day) for four weeks, 29 of 30 patients (97 percent) were cured. Gastrointestinal side effects were frequent (occurring in 62 percent of patients) but mild to moderate in severity, and no patient discontinued therapy because of gastrointestinal side effects. In two patients, treatment was discontinued because of elevated levels of aspartate aminotransferase or creatinine; in both patients the levels rapidly returned to normal. In 12 other patients, the level of aspartate aminotransferase increased to 100 to 150 U per liter during treatment.Conclusions: Orally administered miltefosine appears to be an effective treatment for Indian visceral leishmaniasis. (N Engl J Med 1999;341:1795-800.) (C)1999, Massachusetts Medical Society.