Robledo S M, Valencia A Z, Saravia N G
Centro Internacional de Entrenamiento e Investigaciones Médicas, CIDEIM, Cali, Valle, Colombia.
J Parasitol. 1999 Apr;85(2):360-6.
In vitro sensitivity to pentavalent antimony (SbV) as meglumine antimoniate (Glucantime) of Leishmania of the Viannia subgenus isolated prior to treatment from patients with uncomplicated cutaneous leishmaniasis was evaluated for intracellular amastigotes in the U-937 human monocytic cell line and log phase promastigotes. The 50% effective dose (ED50) of pharmaceutical and additive-free formulations of Glucantime were determined based on the kinetics of the response of Leishmania Viannia to SbV in vitro. ED50 to SbV was inversely related to time of exposure to drug. The potency of the additive-free formulation of Glucantime was significantly greater than that of the pharmaceutical formulation, irrespective of the parasite form. In vitro sensitivity to SbV ranged from < 5.3 micrograms/ml to > 170.0 micrograms/ml. Under the conditions used, 11 (39%) of 28 strains were sensitive to clinically achievable serum concentrations of SbV. No correlation was observed between the total amount of SbV required for healing of lesions and the in vitro response to the pharmaceutical formulation of Glucantime. In contrast, a significant correlation (P = 0.001) was observed between clinical response and the in vitro sensitivity of promastigotes to the additive-free formulation of Glucantime. The greater potency of the additive-free formulation of Glucantime, the correlation of in vitro sensitivity of promastigotes to this formulation and the clinical response to treatment, and the effect of time of exposure to SbV demonstrate the importance of assay conditions on the outcome and interpretation of in vitro evaluation of drug sensitivity.
对来自未合并症皮肤利什曼病患者治疗前分离的维安亚属利什曼原虫，以葡甲胺锑酸盐（葡糖胺锑，Glucantime）形式的五价锑（SbV）进行体外敏感性评估，检测其在U - 937人单核细胞系中的细胞内无鞭毛体和对数期前鞭毛体。基于维安亚属利什曼原虫对SbV体外反应的动力学，确定了葡糖胺锑的药物制剂和无添加剂制剂的50%有效剂量（ED50）。对SbV的ED50与药物暴露时间呈负相关。无论寄生虫形态如何，葡糖胺锑无添加剂制剂的效力均显著高于药物制剂。对SbV的体外敏感性范围为<5.3微克/毫升至>170.0微克/毫升。在所使用的条件下，28株菌株中有11株（39%）对临床可达到的SbV血清浓度敏感。观察到病变愈合所需的SbV总量与对葡糖胺锑药物制剂的体外反应之间无相关性。相反，观察到临床反应与前鞭毛体对葡糖胺锑无添加剂制剂的体外敏感性之间存在显著相关性（P = 0.001）。葡糖胺锑无添加剂制剂的效力更高、前鞭毛体对该制剂的体外敏感性与临床治疗反应之间的相关性以及SbV暴露时间的影响，均表明检测条件对药物敏感性体外评估结果和解释的重要性。
