title: In vitro interactions between new antitubercular drug candidates SQ109 and TMC207.
abstract: 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.
authors.affiliation: Sequella, Inc., 9610 Medical Center Drive, Suite 200, Rockville, MD 20850, USA. venkatareddy@sequella.com
authors.forename: Venkata M
authors.initials: VM
authors.lastname: Reddy
authors.forename: Leo
authors.initials: L
authors.lastname: Einck
authors.forename: K
authors.initials: K
authors.lastname: Andries
authors.forename: Carol A
authors.initials: CA
authors.lastname: Nacy
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology*; D064687:Diarylquinolines; D004347:Drug Interactions; D005029:Ethylenediamines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D005029:Ethylenediamines; C506841:N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine; D011804:Quinolines; C493870:bedaquiline; D000218:Adamantane; D012293:Rifampin
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