{
  "abstract": "Bacteriophage therapy is being explored as an alternate therapeutic approach for treating drug-resistant bacteria, including mycobacteria. However, rational phage dosing remains limited by scarce pharmacokinetic (PK) data and an incomplete understanding of tissue distribution. We performed dose-ranging studies in mice of three therapeutic mycobacteriophages (BPsΔ, ZoeJΔ, Muddy) after intravenous (IV) and intratracheal (IT) administration. All phages behaved similarly. IV dosing produced biphasic kinetics with nonproportional exposure and declining tissue-to-plasma ratios, indicating saturable uptake and elimination. IT delivery yielded monophasic profiles with ∼390-fold higher lung exposure and ∼490-fold lower plasma exposure, supporting inhaled therapy for pulmonary mycobacterial infections. Using BPsΔ data, we developed a mechanistic PBPK model incorporating transcytosis, saturable host clearance, plasma elimination, and lymphatic transport. The model accurately predicted ZoeJΔ and Muddy PK, enabled cross-species extrapolation, and showed that phage morphology influences disposition. This framework advances phage therapy toward model-informed, exposure-guided dose and route selection for multidrug-resistant bacterial infections.",
  "abstract_shown": true,
  "affiliations": [
    "USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, California90033, United States.",
    "Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina27599, United States.",
    "Department of Microbiology & Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina27599, United States.",
    "Engineering and Advanced Technology Department, RTI International, Durham, North Carolina27713, United States.",
    "Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania15260, United States.",
    "Mycobacteria Research Laboratories, Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, Colorado80202, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rajnikant Sharma",
      "orcid": "0000-0002-0891-7548"
    },
    {
      "affs": [
        0
      ],
      "name": "Ramya Mahadevan"
    },
    {
      "affs": [
        0
      ],
      "name": "Sai Divyash"
    },
    {
      "affs": [
        1
      ],
      "name": "Shekhar Yeshwante"
    },
    {
      "affs": [
        0
      ],
      "name": "Saikumar Matcha"
    },
    {
      "affs": [
        0
      ],
      "name": "ChunFu Cheng"
    },
    {
      "affs": [
        2
      ],
      "name": "Hunter S Talley"
    },
    {
      "affs": [
        2
      ],
      "name": "Alan A Schmalstig"
    },
    {
      "affs": [
        2
      ],
      "name": "Pradeep Neupane"
    },
    {
      "affs": [
        3
      ],
      "name": "Sara E Maloney Norcross",
      "orcid": "0000-0003-0114-0550"
    },
    {
      "affs": [
        3
      ],
      "name": "Anthony J Hickey"
    },
    {
      "affs": [
        4
      ],
      "name": "Graham F Hatfull"
    },
    {
      "affs": [
        2,
        5
      ],
      "name": "Miriam Braunstein"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gauri G Rao",
      "orcid": "0000-0002-8704-7770"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/epqwq4rkfcfp4.bib",
  "cited_by": 1,
  "doi": "10.1021/acs.molpharmaceut.6c00604",
  "fulltext_url": "https://europepmc.org/articles/PMC13693667",
  "id": "epqwq4rkfcfp4",
  "issns": [
    "1543-8384",
    "1543-8392"
  ],
  "landing_url": "https://europepmc.org/article/MED/42906173",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2303|Bacteriophages and microbial interactions"
    ]
  ],
  "openalex": "W7213432563",
  "pdf_url": "https://europepmc.org/articles/PMC13693667?pdf=render",
  "pmcid": "PMC13693667",
  "pmid": "42906173",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/epqwq4rkfcfp4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42906173",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42906173"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2303|Bacteriophages and microbial interactions",
      "subfield": "ecology"
    }
  ],
  "title": "Pharmacokinetics and Physiologically Based Pharmacokinetic Modeling of Mycobacteriophages: Insights into Pulmonary Distribution and Clearance.",
  "title_text": "Pharmacokinetics and Physiologically Based Pharmacokinetic Modeling of Mycobacteriophages: Insights into Pulmonary Distribution and Clearance.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/epqwq4rkfcfp4",
  "venue": "Molecular pharmaceutics",
  "versions": []
}