Sowunmi A, Fehintola F A, Ogundahunsi O A, Oduola A M
Department of Pharmacology and Therapeutics, University of Ibadan, Nigeria.
Trans R Soc Trop Med Hyg. 1998 Jul-Aug;92(4):441-5. doi: 10.1016/s0035-9203(98)91084-7.
In the face of growing chloroquine resistance of Plasmodium falciparum, efforts to prolong the clinical usefulness of the drug have partly concentrated on its combination with potential resistance-reversing compounds. However, clinical studies on such combinations have been limited. We have compared the efficacy of halofantrine, an arylaminoalcohol effective in chloroquine resistant malaria, and a combination of chloroquine plus chlorpheniramine, a histamine H1 receptor antagonist which reverses chloroquine resistance of P. falciparum in vitro and in vivo, in 100 children with acute symptomatic uncomplicated falciparum malaria in an area in Nigeria where the rate of chloroquine resistance is 35-45%. Both chloroquine plus chlorpheniramine and halofantrine produced similar parasite and fever clearance times and cure rates (96%). Both treatment regimens were relatively well tolerated. Pruritus was commoner in patients treated with chloroquine plus chlorpheniramine than in those treated with halofantrine. Intravascular haemolysis occurred in one patient, and abdominal pain with or without diarrhoea occurred in 4 patients, treated with halofantrine. In vitro, the chloroquine resistance of P. falciparum isolates obtained from the patients was reversed by verapamil. All patients with isolates which were chloroquine-resistant in vitro were cured by either therapy. These results indicate that chloroquine plus chlorpheniramine is as effective as halofantrine and is without overt deleterious effect in treating acute uncomplicated chloroquine-resistant falciparum malaria in children, and may be a clinically useful alternative for this purpose in Nigeria.
面对恶性疟原虫对氯喹的耐药性不断增加,延长该药物临床效用的努力部分集中在将其与潜在的耐药性逆转化合物联合使用上。然而,关于此类联合用药的临床研究一直有限。在尼日利亚一个氯喹耐药率为35%-45%的地区,我们比较了卤泛群(一种对氯喹耐药疟疾有效的芳基氨基醇)以及氯喹加氯苯那敏(一种组胺H1受体拮抗剂,在体外和体内均可逆转恶性疟原虫对氯喹的耐药性)对100例急性症状性非复杂性恶性疟儿童的疗效。氯喹加氯苯那敏和卤泛群产生了相似的寄生虫清除时间、发热清除时间和治愈率(96%)。两种治疗方案的耐受性都相对良好。氯喹加氯苯那敏治疗的患者比卤泛群治疗的患者瘙痒更为常见。接受卤泛群治疗的1例患者发生血管内溶血,4例患者出现腹痛伴或不伴腹泻。在体外,维拉帕米可逆转从患者分离出的恶性疟原虫分离株对氯喹的耐药性。所有体外对氯喹耐药的分离株患者均通过两种治疗方法治愈。这些结果表明,氯喹加氯苯那敏在治疗儿童急性非复杂性氯喹耐药恶性疟疾方面与卤泛群一样有效,且无明显有害作用,在尼日利亚可能是用于此目的的一种临床上有用的替代药物。