Is chloroquine making a comeback?
Is chloroquine making a comeback?
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氯喹会卷土重来吗？
DOI：
10.1093/infdis/jiq002
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Meshnick,StevenR
中科院分区：
文献类型：
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作者：
Hand,CarlaCerami;Meshnick,StevenR
几十年来，氯喹一直是一种非常有效、安全和廉价的抗疟药。对氯喹有效性的乐观态度使公共卫生专业人员预测到2000年将消灭疟疾[1]。到1979年，相当于。每年使用5亿片氯喹[2]。不幸的是，恶性疟原虫逐渐对氯喹产生抗药性。在20世纪50年代末首次出现在东南亚和南美洲后，耐药性在80年代蔓延到整个非洲[3]。与此同时，替代抗疟疾药物更昂贵，尽管有证据表明氯喹无效，但许多国家仍继续使用氯喹。认识到这一点导致了对世界卫生组织和世界银行的渎职指控，并大力推动用更有效的青蒿素联合疗法取代氯喹[4]。氯喹能卷土重来吗？来自马拉维的证据表明，氯喹在停用十年后抗药性消失，恢复了该药物的临床疗效[5]。此外，Ursing等人提出的证据[6]表明，即使在存在氯喹耐药性的情况下，改变给药方案也能恢复疗效。Ursing等人[6]在本期《传染病杂志》和以前的文章[7-8]中报告说，通过每天给药两次而不是每天一次，可以降低体内氯喹失败率。以这种方式将氯喹的常用剂量增加一倍，尽管先前存在氯喹耐药性，但治愈率仍很高(95%)，并且没有导致不良事件的增加。有趣的是，这些作者还表明，在几内亚比绍使用这种改进的氯喹剂量方案，通过pfcrt 76T的流行率[7，9-10]来衡量，已经稳定了氯喹耐药性的传播。这种疗效的提高可以用氯喹的药代动力学来解释。氯喹可以渗透大多数组织(如脑、眼、心、肾、白细胞、肝、肺和脾)，因此具有很大的分布体积[11]。口服后，氯喹85%在血浆中被吸收，血浆浓度在1-2小时内达到峰值，然后
For decades, chloroquine was a remarkably effective, safe, and inexpensive antimalarial. Optimism about effectiveness of chloroquine led public health professionals to predict the eradication of malaria by 2000 [1]. By 1979, the equivalent of. 500 million tablets of chloroquine were used each year [2]. Unfortunately, Plasmodium falciparum gradually became resistant to chloroquine. After first appearing in Southeast Asia and South America in the late 1950s, resistance spread throughout Africa by the 1980s [3]. Meanwhile, alternative antimalarials were more expensive, and many countries continued to use chloroquine despite evidence that it was not effective. Recognition of this led to accusations of malpractice against the World Health Organization and theWorld Bank and a vigorous drive to replace chloroquine with more-effective artemisinin combination therapies [4]. Can chloroquine make a comeback? Evidence from Malawi suggests that chloroquine resistance faded a decade after it was withdrawn from use, restoring the clinical efficacy of the drug [5]. In addition, evidence presented by Ursing et al [6] suggests that, even in the presence of chloroquine resistance, a change in the dosing regimen restores efficacy. Ursing et al.[6] reported in this issue of The Journal of Infectious Diseases and in previous articles [7-8] that the in vivo chloroquine failure rate can be decreased by giving the drug twice per day instead of once per day. Doubling the frequently used dose of chloroquine in this way achieved a high cure rate (95%) despite preexisting chloroquine resistance and did not result in an increase in adverse events. Of interest, these authors also showed that use of this modified chloroquine dosing regimen in Guinea-Bissau has stabilized the spread of chloroquine resistance, as measured by the prevalence of pfcrt 76T [7, 9–10]. This increase in efficacy can be explained by the pharmacokinetics of chloroquine. Chloroquine can penetrate most tissues (eg, brain, eyes, heart, kidneys, leukocytes, liver, lungs, and spleen) and, therefore, has a large volume of distribution [11]. After oral administration, chloroquine is 85% absorbed in the plasma, with a time to peak plasma levels of 1–2 h, and then it is