Palmer K J, Holliday S M, Brogden R N
Adis International Limited, Auckland, New Zealand.
Drugs. 1993 Mar;45(3):430-75. doi: 10.2165/00003495-199345030-00009.
Mefloquine is an orally administered blood schizontocide. Initial dose-finding and comparative studies performed between 1977 and 1989 demonstrated efficacy of mefloquine as prophylaxis in nonimmune individuals and in the suppression and treatment of malaria in adults and children caused by multidrug-resistant Plasmodium falciparum. It was also effective against P. vivax infection, while data concerning the treatment of P. ovale and P. malariae infections were limited. In an attempt to delay the emergence of resistance to this promising antimalarial agent, mefloquine was combined with sulfadoxine and pyrimethamine. Although initial clinical trials indicated that this regimen was effective in preventing and treating falciparum malaria, recent treatment failures, the potential for severe dermatological reactions and lack of therapeutic advantage over mefloquine alone has prompted the World Health Organization to recommended that the combination be no longer used for treatment or prophylaxis of malaria. Mefloquine is generally well tolerated in both adults and children, with nausea, vomiting, diarrhoea, headache, dizziness, rash, pruritus and abdominal pain being the most common adverse effects, although it is difficult to distinguish between disease- and treatment-related events. The incidence of these adverse effects is similar to or lower than those observed with other antimalarial agents. Cardiovascular changes, such as bradycardia, occasionally occur. The most notable adverse effects associated with mefloquine are neuropsychiatric disturbances; precipitation of such events should be closely monitored and requires termination of prophylaxis or therapy. The eventual emergence of resistance to mefloquine, as with many other antimalarial agents, was inevitable. Mefloquine resistance is established in certain areas of Thailand and may be becoming a growing problem in other regions of the world. In order to preserve the efficacy of mefloquine in non-resistant areas, this useful agent should be used with care and only prescribed for prophylaxis in travellers and treatment in areas of multidrug-resistant plasmodia. Future options to combat mefloquine resistance may include the combination of mefloquine with other antimalarial agents such as qinghaosu derivatives. Thus, with cautious use and possible combination with other agents, mefloquine is likely to remain an important treatment option for falciparum malaria, a widespread parasitic disease for which an increasing number of drugs have proved inadequate.
甲氟喹是一种口服血液裂殖体杀灭剂。1977年至1989年进行的初始剂量探索和比较研究表明，甲氟喹对非免疫个体有预防作用，对耐多药恶性疟原虫引起的成人和儿童疟疾有抑制和治疗作用。它对间日疟原虫感染也有效，而关于卵形疟原虫和三日疟原虫感染治疗的数据有限。为了延缓对这种有前景的抗疟药物产生耐药性，甲氟喹与磺胺多辛和乙胺嘧啶联合使用。尽管最初的临床试验表明该方案对预防和治疗恶性疟有效，但最近出现的治疗失败、严重皮肤反应的可能性以及相对于单独使用甲氟喹缺乏治疗优势，促使世界卫生组织建议不再将该联合用药用于疟疾的治疗或预防。甲氟喹在成人和儿童中一般耐受性良好，最常见的不良反应是恶心、呕吐、腹泻、头痛、头晕、皮疹、瘙痒和腹痛，不过很难区分与疾病相关和与治疗相关的事件。这些不良反应的发生率与其他抗疟药物相似或更低。心血管变化，如心动过缓，偶尔会发生。与甲氟喹相关的最显著不良反应是神经精神障碍；应密切监测此类事件的发生，必要时需终止预防或治疗。与许多其他抗疟药物一样，对甲氟喹最终产生耐药性是不可避免的。泰国某些地区已出现甲氟喹耐药性，在世界其他地区这可能也正成为一个日益严重的问题。为了在非耐药地区保持甲氟喹的疗效，应谨慎使用这种有用的药物，仅用于旅行者预防和耐多药疟原虫地区的治疗。对抗甲氟喹耐药性的未来选择可能包括将甲氟喹与其他抗疟药物如青蒿素衍生物联合使用。因此，谨慎使用并可能与其他药物联合使用，甲氟喹可能仍然是治疗恶性疟的重要选择，恶性疟是一种广泛传播的寄生虫病，越来越多的药物已被证明对其治疗效果不佳。
