氟西汀可增强氯喹和甲氟喹在体外对多重耐药恶性疟原虫的作用。

Fluoxetine potentiates chloroquine and mefloquine effect on multidrug-resistant Plasmodium falciparum in vitro.

作者信息

Khairul Mohd Fadzli Mustaffa, Min Tan Hooi, Low Jen Hou, Nasriyyah Che Husin Che, A'shikin Azahri Noor, Norazmi Mohd Nor, Ravichandran Manickam, Raju Suraparaju Sivachandra

机构信息

Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

出版信息

Jpn J Infect Dis. 2006 Oct;59(5):329-31.

PMID:17060702

Abstract

Fluoxetine (FLX), a P-glycoprotein inhibitor with antimalarial activity, is promising candidate for reversing chloroquine/mefloquine (CQ/MQ) resistance. The Dd2 strain of CQ- and MQ-resistant Plasmodium falciparum was synchronized and assayed with various concentrations of CQ/MQ individually and in combination with FLX or verapamil (VPL). Our results indicated the 50% inhibitory concentration values of CQ and MQ were greatly lowered when FLX was used simultaneously. Isobolograms indicated that CQ-FLX combinations are more synergistic (mean fractional inhibitory concentration [FIC] index 0.55) than MQ-FLX (mean FIC index 0.64), and their synergistic effect was better than or at par with CQ-VPL (mean FIC index 0.88) and MQ-VPL (mean FIC index 0.60) combinations. We conclude that the FLX potentiates the CQ and MQ response on multidrug-resistant P. falciparum at clinically achievable concentrations.

摘要

氟西汀（FLX）是一种具有抗疟活性的P-糖蛋白抑制剂，是逆转氯喹/甲氟喹（CQ/MQ）耐药性的有前景的候选药物。对CQ和MQ耐药的恶性疟原虫Dd2株进行同步化处理，并分别用不同浓度的CQ/MQ以及与FLX或维拉帕米（VPL）联合进行测定。我们的结果表明，当同时使用FLX时，CQ和MQ的50%抑制浓度值大大降低。等效线图表明，CQ-FLX组合比MQ-FLX组合更具协同性（平均分数抑制浓度[FIC]指数为0.55），并且它们的协同效应优于或等同于CQ-VPL（平均FIC指数为0.88）和MQ-VPL（平均FIC指数为0.60）组合。我们得出结论，在临床可达到的浓度下，FLX可增强CQ和MQ对多重耐药恶性疟原虫的反应。