{
  "abstract": "TBAJ-587 is a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile than the first-generation bedaquiline. It is currently under development for the treatment of drug-susceptible and drug-resistant tuberculosis. A first-in-human trial of TBAJ-587, including single and multiple ascending oral doses and a dedicated food-effect cohort, was conducted in 92 healthy adults. Plasma exposures of TBAJ-587 were generally linear for AUCtau and slightly subproportional for Cmax, with the major circulating active metabolite, M3, remaining low relative to the parent. A high-fat meal increased the mean Cmax and AUClast 3.46- and 2.26-fold, respectively. TBAJ-587 accumulated with multiple dosing over the 28-day period, with mean accumulation ratios across the three tested doses ranging from 1.69 to 2.32 for Cmax and from 2.74 to 3.73 for AUCtau. However, steady-state conditions were not yet reached on day 28. Mean terminal half-lives after 28-day dosing of TBAJ-587 ranged from approximately 80 to 111 days. There were no deaths or serious adverse events, and TBAJ-587 was generally safe and well tolerated at single doses of 25–800 mg under fasting conditions and multiple doses of 50–200 mg once daily for 28 days after a standard breakfast. In addition, no dose- or time-dependent effects were noted for any of the other safety and tolerability parameters, including no clinically significant effects on the QTc interval. These results support further investigation of TBAJ-587 for the treatment of tuberculosis.\n\nCLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04890535.",
  "abstract_shown": true,
  "affiliations": [
    "Global Alliance for TB Drug Development, New York, New York, USA",
    "QPS Netherlands BV, Groningen, the Netherlands",
    "Vast Therapeutics, Morrisville, North Carolina, USA",
    "IdiPAZ, University Hospital La Paz, Servicio Madrileño de Salud (SERMAS), Madrid, Spain",
    "Department of Clinical Pharmacy and Pharmacology, University Medical Center, Groningen, the Netherlands"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jerry Nedelman",
      "orcid": "0000-0002-0205-522X"
    },
    {
      "affs": [
        0
      ],
      "name": "Almari Conradie"
    },
    {
      "affs": [
        0
      ],
      "name": "Antonio Lombardi",
      "orcid": "0009-0001-7383-2495"
    },
    {
      "affs": [
        0
      ],
      "name": "Dean Hickman",
      "orcid": "0009-0003-6761-9764"
    },
    {
      "affs": [
        1
      ],
      "name": "Khalid Abd-Elaziz"
    },
    {
      "affs": [
        1
      ],
      "name": "Peter Dogterom"
    },
    {
      "affs": [
        2
      ],
      "name": "Paul Bruinenberg"
    },
    {
      "affs": [
        3
      ],
      "name": "Antonio J. Carcas Sansuán"
    },
    {
      "affs": [
        1
      ],
      "name": "Elly Sakiman"
    },
    {
      "affs": [
        4
      ],
      "name": "Zuzana Diamant",
      "orcid": "0000-0003-0133-0100"
    },
    {
      "affs": [
        1
      ],
      "name": "Jolanda van Duinen"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Beumont",
      "orcid": "0000-0001-6298-2482"
    },
    {
      "affs": [
        0
      ],
      "name": "Eugene Sun",
      "orcid": "0009-0009-2326-0570"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0ahfmy0wygryw.bib",
  "cited_by": 1,
  "doi": "10.1128/aac.01930-25",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13712999/",
  "id": "0ahfmy0wygryw",
  "issns": [
    "0066-4804",
    "1098-6596"
  ],
  "landing_url": "https://doi.org/10.1128/aac.01930-25",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Pharmacology"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7171522127",
  "pdf_url": "https://journals.asm.org/doi/pdf/10.1128/aac.01930-25?download=true",
  "pmcid": "PMC13712999",
  "pmid": "42520186",
  "published": "2026-07-28",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/0ahfmy0wygryw.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:28Z",
      "native_id": "PMC13712999",
      "source": "pmc",
      "url": "https://doi.org/10.1128/aac.01930-25"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "heading:Pharmacology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants",
  "title_text": "Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:23:28Z",
  "url": "https://research.draconitic.com/paper/0ahfmy0wygryw",
  "venue": "Antimicrobial Agents and Chemotherapy",
  "versions": []
}