新型抗结核候选药物 SQ109 和 TMC207 的体外相互作用。
In vitro interactions between new antitubercular drug candidates SQ109 and TMC207.
机构信息
Sequella, Inc., 9610 Medical Center Drive, Suite 200, Rockville, MD 20850, USA.
出版信息
Antimicrob Agents Chemother. 2010 Jul;54(7):2840-6. doi: 10.1128/AAC.01601-09. Epub 2010 Apr 12.
The in vitro interactions of two new antitubercular drugs, SQ109 and TMC207, with each other and with rifampin (RIF) were evaluated. The combination of SQ109 with TMC207 (i) improved an already excellent TMC207 MIC for M. tuberculosis H37Rv by 4- to 8-fold, (ii) improved the rate of killing of bacteria over the rate of killing by each single drug, and (iii) enhanced the drug postantibiotic effect by 4 h. In no instance did we observe antagonistic activities with the combination of SQ109 and TMC207. Rifampin activates cytochrome P450 genes to reduce the area under the curve (AUC) for TMC207 in humans. The presence of RIF in three-drug combinations did not affect the synergistic activities of SQ109 and TMC207, and SQ109 also dramatically decreased the MIC of RIF. SQ109 was active by itself, and both its activity was improved by and it improved the in vitro activities of both RIF and TMC207.
我们评估了两种新的抗结核药物 SQ109 和 TMC207 彼此之间以及与利福平（RIF）的体外相互作用。SQ109 与 TMC207 的联合应用（i）将 TMC207 对结核分枝杆菌 H37Rv 的 MIC 提高了 4 至 8 倍，（ii）提高了细菌的杀菌率，超过了每种单一药物的杀菌率，（iii）增强了药物的抗生素后效应达 4 小时。在任何情况下，我们都没有观察到 SQ109 和 TMC207 联合应用的拮抗活性。利福平激活细胞色素 P450 基因，降低人类 TMC207 的 AUC。RIF 存在于三联药物组合中并不影响 SQ109 和 TMC207 的协同作用，SQ109 也显著降低了 RIF 的 MIC。SQ109 本身具有活性，它提高了 RIF 和 TMC207 的体外活性，同时也提高了自身的活性。
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