Mitigation of the haemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Piasmodium vivax by intermittent regimens of drug administration: a preliminary report.
Mitigation of the haemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Piasmodium vivax by intermittent regimens of drug administration: a preliminary report.
复制标题
DOI：
--
复制
发表时间：
1960
影响因子：
11.1
通讯作者：
A. Alving;Charles F. Johnson;A. Tarlov;G. Brewer;Kellermeyer Rw;P. Carson
中科院分区：
文献类型：
--
作者：
A. Alving;Charles F. Johnson;A. Tarlov;G. Brewer;Kellermeyer Rw;P. Carson
伯氨喹是一种8-氨基喹啉衍生物，是对抗疟疾寄生虫组织阶段最有效的药物之一。不幸的是，某些人患有遗传性代谢缺陷，这使他们在摄入8-氨基喹啉、某些其他药物和某些蔬菜后容易发生溶血。易感性似乎是由一个可变表达的部分显性性连锁基因遗传的。在这种缺陷完全表达的人，血管内溶血可能严重到类似黑水热。有研究表明，每日剂量的伯氨喹引起的溶血是自限性的，只要这种剂量不过量，因为年轻的红细胞对药物的破坏具有相对的抵抗力。本论文中报告的治疗研究表明，每周给药（连同氯喹或其同系物的标准抑制剂量）可显著降低毒性，同时提高其根治切森间日疟疾的治疗效果。每周服用45毫克伯氨喹，连续服用8周，对严重的切森间日疟原虫感染非常有效。它治愈了90%的感染，但在对伯氨喹敏感且主要表达溶血特征的成年男性中没有产生临床明显的溶血。
Primaquine-an 8-aminoquinoline derivative-is one of the most effective drugs for use against the tissue stages of the malaria parasite. Unfortunately certain persons suffer from an inherited defect of metabolism which renders them susceptible to haemolysis after ingestion of the 8-aminoquinolines, certain other drugs and some vegetables. Susceptibility appears to be inherited by a partially dominant sex-linked gene of variable expression. In persons with full expression of this defect, intravascular haemolysis may be of such severity as to mimic blackwater fever.It has been shown that the haemolysis caused by daily doses of primaquine is self-limited, provided that such doses are not excessive, by virtue of the fact that the younger erythrocytes are relatively resistant to destruction by the drug.Therapeutic studies reported in the present paper indicate that the toxicity is markedly diminished by regimens requiring administration in weekly doses (together with the standard suppressive dose of chloroquine or one of its congeners) while its therapeutic effectiveness in the radical cure of Chesson vivax malaria is increased.A weekly dose of 45 mg primaquine proved highly effective against severe Chesson vivax infections when administered for eight weeks. It cured 90% of infections, yet did not produce clinically demonstrable haemolysis in primaquine-sensitive adult males with major expression of the haemolytic trait.