1393. A Phase 1, Randomized, Open-Label, Crossover Study in Healthy Subjects under Fasting Conditions of Orally Administered Sulopenem Etzadroxil Alone or with Probenecid to Determine the Pharmacokinetics of Sulopenem.
Session: Poster Abstract Session: PK/PD Studies
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • 102 poster Final.pdf (73.2 kB)
  • Background: Antimicrobial resistance to available oral antibiotics is becoming progressively more common, precipitating the need for additional treatment options as step‐down from initial intravenous (IV) therapy as well as for treatment of infections in the community. Sulopenem (CP‐70,429) is a thiopenem antibiotic active against quinolone non‐susceptible and ESBL‐producing Enterobacteriaceae. As the key pharmacokinetic‐pharmacodynamic variable correlating with efficacy for penem antibiotics is time above minimum inhibitory concentration (T>MIC), we examined the utility of probenecid, an OAT‐1 inhibitor of β‐lactam excretion, on the pharmacokinetic (PK) parameters for the oral prodrug of sulopenem, sulopenem etzadroxil

    Methods: Twelve healthy males and females received a single oral dose of 500 mg sulopenem etzadroxil as powder in bottle either alone or co‐administered with a single oral dose of probenecid 500 mg in a crossover design with a washout period of 6 days. All doses were administered under fasting conditions. Blood samples for plasma PK analysis were collected and PK parameters for sulopenem, the parent compound of sulopenem etzadroxil, were determined.

    Results:

    Treatment

    N

    Sulopenem Parameter (Day 1; mean)

    Cmax

    (ng/mL)

    AUC0‐INF

    (hr*ng/mL)

    T>MIC

    (0.5 µg/mL) [hr]

    T> MIC

    (0.5 µg/mL) [%, 12 hr interval]

    500 mg sulopenem etzadroxil

    10

    1928

    3871

    2.8

    23.3

    500 mg sulopenem etzadroxil

    + 500 mg probenecid

    11

    1929

    4964

    3.6

    30.2

    Conclusion: Probenecid increases the AUC of sulopenem by 28% in the fasted state and extends the mean time over MIC.

    Michael Dunne, MD1, Steven Aronin, MD1, Elise Dunzo, Ph.D2 and Sailaja Puttagunta, MD1, (1)Iterum Therapeutics, Old Saybrook, CT, (2)Parexel International, Baltimore, MD

    Disclosures:

    M. Dunne, Iterum Therapeutics: Employee and Shareholder , Salary .

    S. Aronin, Iterum Therapeutics: Employee and Shareholder , Salary .

    E. Dunzo, Parexel: Consultant , Consulting fee .

    S. Puttagunta, Iterum Therapeutics: Employee and Shareholder , Salary .

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