Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs

Memórias do Instituto Oswaldo Cruz

Juliana Quero Reimão¹  André Gustavo Tempone¹ 

[1] ,Instituto Adolfo Lutz Departamento de Parasitologia São Paulo SP ,Brasil

关键词: leishmaniasis;    Leishmania therapy;    calcium channel blockers;    drug combinations;    isobologram;   

DOI  :  10.1590/S0074-02762011000800022

来源: SciELO

【 摘 要 】

The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of FICs (ΣFICs) and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.

【 授权许可】

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