{
    "abstract": "To use animal pharmacokinetic data and FluidSIM modeling to estimate human dexamethasone perilymph concentrations from plasma concentration measurements over time following a single intratympanic administration of SPT-2101.\nPerilymph and plasma dexamethasone concentrations were measured in guinea pigs and African green monkeys over 3 to 6 weeks post-intratympanic administration of SPT-2101. Plasma concentrations of dexamethasone were measured in M\u00e9ni\u00e8re's disease patients post-intratympanic administration of SPT-2101. FluidSIM was trained on the correlations of animal plasma and animal perilymph levels, allowing the human perilymph drug time course for SPT-2101 to be predicted from measured human plasma dexamethasone concentrations.\nTertiary care neurotology clinic in Perth, Australia.\nNine adults with unilateral definite M\u00e9ni\u00e8re's disease per Barany Society criteria.\nIntratympanic SPT-2101, a single injection of a long-acting gel formulation of dexamethasone precisely delivered at the round window.\nEstimated dexamethasone levels in human perilymph following a single administration of SPT-2101 at the round window over time.\nPerilymph dexamethasone concentrations were above estimated therapeutic levels for up to 35 days in guinea pigs and at least 21 days in African green monkeys. In human subjects, plasma dexamethasone concentrations were detected for 2 weeks post-administration. Animal middle ear, plasma and perilymph drug interrelationships were compared to FluidSIM simulations, providing rationale for correlating dexamethasone concentrations in the respective compartments. Comparable simulations of human plasma concentrations predicted perilymph dexamethasone therapeutic levels in humans for 23-55 days.\nSustained release dexamethasone from SPT-2101 precisely delivered at the round window provides prolonged and durable estimated perilymph concentrations in clinical subjects.",
    "authors": [
        {
            "affiliation": "Spiral Therapeutics, Inc., South San Francisco, California, USA.",
            "firstname": "Benson T",
            "initials": "BT",
            "lastname": "Jung"
        },
        {
            "affiliation": null,
            "firstname": "Jafri",
            "initials": "J",
            "lastname": "Kuthubutheen"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, USA.",
            "firstname": "Jeffrey D",
            "initials": "JD",
            "lastname": "Sharon"
        },
        {
            "affiliation": "Jobral Consulting, San Diego, California, USA.",
            "firstname": "Alan C",
            "initials": "AC",
            "lastname": "Foster"
        },
        {
            "affiliation": null,
            "firstname": "Signe",
            "initials": "S",
            "lastname": "Erickson"
        },
        {
            "affiliation": "Spiral Therapeutics, Inc., South San Francisco, California, USA.",
            "firstname": "Hugo",
            "initials": "H",
            "lastname": "Peris"
        },
        {
            "affiliation": "Spiral Therapeutics, Inc., South San Francisco, California, USA.",
            "firstname": "Eugene",
            "initials": "E",
            "lastname": "De Juan"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, USA.",
            "firstname": "Charles J",
            "initials": "CJ",
            "lastname": "Limb"
        },
        {
            "affiliation": "Spiral Therapeutics, Inc., South San Francisco, California, USA.",
            "firstname": "Kathleen Cogan",
            "initials": "KC",
            "lastname": "Farinas"
        },
        {
            "affiliation": "Turner Scientific, Inc., Jacksonville, Illinois, USA.",
            "firstname": "Jeremy",
            "initials": "J",
            "lastname": "Turner"
        },
        {
            "affiliation": "Turner Scientific, Inc., Jacksonville, Illinois, USA.",
            "firstname": "Amanda",
            "initials": "A",
            "lastname": "Henton"
        },
        {
            "affiliation": "Turner Scientific, Inc., Jacksonville, Illinois, USA.",
            "firstname": "Alec",
            "initials": "A",
            "lastname": "Salt"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.",
    "doi": "10.1097/MAO.0000000000004336",
    "journal": "Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology",
    "keywords": [],
    "methods": null,
    "publication_date": "2024-11-26",
    "pubmed_id": "39589784",
    "results": "Perilymph dexamethasone concentrations were above estimated therapeutic levels for up to 35 days in guinea pigs and at least 21 days in African green monkeys. In human subjects, plasma dexamethasone concentrations were detected for 2 weeks post-administration. Animal middle ear, plasma and perilymph drug interrelationships were compared to FluidSIM simulations, providing rationale for correlating dexamethasone concentrations in the respective compartments. Comparable simulations of human plasma concentrations predicted perilymph dexamethasone therapeutic levels in humans for 23-55 days.",
    "title": "Plasma Concentration as a Proxy for Perilymph Drug Levels: Preclinical and Clinical Dexamethasone Measures with a Long-Acting Formulation for Precise Delivery to the Round Window Membrane.",
    "xml": "<Element 'PubmedArticle' at 0x788506aaf2e0>"
}