López-Antuñano F J
Instituto Nacional de Salud Pública, Avenida Universidad 655, colonia Santa María Ahuacatitlán, 62508 Cuernavaca, Morelos, México.
Salud Publica Mex. 1999 Sep-Oct;41(5):410-9. doi: 10.1590/s0036-36341999000500010.
The main objective of this paper is to make available in a single document, a sequence of events that have been published on the biology of malaria parasites and their interaction with the human host, looking for arguments for effective and save treatment: what we know and what we would like to know about the effects of primaquine in order to justify its use in clinical and public health practice. The practicioner should be aware that the antimalarial activity, hemolytic and methemoglobinemic side effects, and detoxification of primaquine are all thought to depend on various biotransformation products of the drug. In spite of the universal use during over six decades, their site and mechanism of formation and degradation and their specific biologic effects remain very poorly understood in human beings. The mature gametocytes of P. falciparum are naturally resistant to chloroquine and other blood merontocides, but they are usually eliminated with a single dose of 1.315 mg/kg per os (p.o.) of primaquine phosphate (equivalent to 0.75 mg-base). Rather than empirically, related with relapses frequency, dosage schedules should only be determined through consideration of the kinetics and dynamics of the drug and its effect on sporozoites, pre and exo-erythrocytic merontes, hypnozoites and gametocytes of P. vivax. Where medical care services are not available or not capable to detect glucose-6-phosphate dehydrogenese- (G-6-PD) deficiencies and deleterious effects of the drug, we recommend not to use primaquine. Both, P. vivax primary clinical attack and P. vivax relapses, as and when they occur should be treated with a course of 10 mg/kg chloroquine-base p.o. Prevention of relapses is probably related to strain characteristics of P. vivax hypnozoites populations involved. If well informed and qualified medical care workers decide to use primaquine in the absence of enzime deficiencies and are able to follow-up the clinical, toxicological and parasitic results, a daily dose of 0.25 mg/kg primaquine-base during 14 days could be administered safety for possible prevention of P. vivax relapses.
本文的主要目的是在一份文件中呈现一系列已发表的关于疟原虫生物学及其与人类宿主相互作用的事件，寻找有效且安全治疗的依据：我们所知道的以及我们想要了解的关于伯氨喹作用的信息，以便证明其在临床和公共卫生实践中的应用合理性。从业者应意识到，伯氨喹的抗疟活性、溶血和高铁血红蛋白血症副作用以及解毒作用都被认为取决于该药物的各种生物转化产物。尽管在六十多年里一直广泛使用，但它们在人体内的形成和降解部位及机制以及特定生物学效应仍知之甚少。恶性疟原虫的成熟配子体对氯喹和其他血液内裂殖体杀灭剂天然耐药，但通常用1.315毫克/千克口服磷酸伯氨喹（相当于0.75毫克碱基）单剂量即可清除。剂量方案不应凭经验、依据复发频率来确定，而应通过考虑药物的动力学和动态过程及其对间日疟原虫子孢子、前红细胞内期和红细胞外期裂殖体、休眠子和配子体的作用来确定。在无法获得医疗服务或无法检测葡萄糖 - 6 - 磷酸脱氢酶（G - 6 - PD）缺乏症及药物有害作用的地方，我们建议不要使用伯氨喹。间日疟原虫的初次临床发作和复发一旦发生，均应以10毫克/千克碱基的氯喹口服一个疗程进行治疗。复发的预防可能与所涉及的间日疟原虫休眠子群体的菌株特征有关。如果消息灵通且资质合格的医护人员在不存在酶缺乏症的情况下决定使用伯氨喹，并能够跟踪临床、毒理学和寄生虫学结果，那么每天0.25毫克/千克碱基的伯氨喹连续服用14天可安全给药，有可能预防间日疟原虫复发。
