Pharmacokinetics, Pharmacodynamics, & Drug Metabolism Community

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  • 1.  PPDM and Emerging Modalities

    Community Leadership
    Posted 04-17-2023 17:37

    With the rapid advancement of therapeutics, new technologies and treatment modalities are being developed to meet the unique needs of patients. Personalized medicine has been evolving with the chemical modalities researchers are focusing on including gene therapy, antibody drug conjugates, next generation peptides, protein degraders, and RNA-based therapy to address "difficult" diseases. In light of this, how are you applying PPDM for emerging modalities at your current role? 



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    Alexandria Senetra
    PhD Student
    University of Florida College of Pharmacy
    Gainesville FL
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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  • 2.  RE: PPDM and Emerging Modalities

    Community Leadership
    Posted 04-27-2023 19:14

    Alexandria, thank you for the interesting question.
    CNS is one of the most challenging disease areas for multiple reasons. Among various strategies, peptides present promising strategy to overcome the obstacle posed by the blood brain barrier (BBB) and its potential to be developed as long-acting injectables.





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    Pankajini Mallick PhD
    Principal Scientist, Preclinical Pharmacokinetics | DMPK
    San Diego CA


    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 3.  RE: PPDM and Emerging Modalities

    Community Leadership
    Posted 08-13-2023 15:21

    Thanks Alexandria, based on my experience PPDM strategically help bridges the gap to support drug development and regulatory approvals. Understanding the drug exposure–response relationship lies at the heart of bridging the gap that enables a dose selection decision by balancing effectiveness and safety. Furthermore, PPDM tools helps understand the influence of intrinsic and extrinsic factors on drug pharmacokinetics that enables dose adjustment decisions based on drug exposures. At my previous projects I have seen/applied PPDM/Clinical Pharmacology approaches to identify doses and regimens without a formal dose-finding study, the support of new doses and regimens without conducting additional studies, and the extrapolation of adult drug–drug interaction (DDI) studies to pediatrics without performing a pediatric DDI study. 



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    Rakesh Gollen Ph.D.

    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 4.  RE: PPDM and Emerging Modalities

    Community Leadership
    Posted 08-14-2023 08:48

    Great question @Alexandria Senetra!  Those of us that have transitioned from the traditional small molecule/chemical modality to newer therapeutic modalities are finding that the traditional assays to assess ADME/DMPK parameters for better PK/PD and IVIVE predictions are running into many challenging physicochemical properties with these newer modalities.  Significant challenges such non-specific binding, poor solubility, or poor analytical signals, are barriers in data interpretation using traditional ADME assays.  Newer mechanistic models, such as, organ-on-a-chip/Multi-organ physiologic systems (MPS), may be able to provide some more translational data than the traditional assays.

    I would like to hear what other in vitro models or assays others have tried to develop to assess this gap in IVIVE.

    Best regards,

    Steven-



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    Steven Louie M.S.
    Associate Director
    Moderna
    Cambridge MA
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 5.  RE: PPDM and Emerging Modalities

    Community Leadership
    Posted 08-14-2023 21:14

    Hi Alexandria and all, this is an excellent question and I think the answers would be evolving as much as the novel modalities are. I believe much of the principles of PPDM still apply but we have to diligently assess what we are measuring and how the data relates to the mechanism of action. Just as Steven mentioned, traditional assays might not give the same answer due to confounding factors so there may be cases where we shouldn't apply the same method/equation as traditional modalities. That goes same for clinical data since we have to re-evaluate what we are measuring in the samples and how to interpret them. Overall, I'd say that PPDM's role became more important, not less, with the newer modalities!!



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    Jong Bong Lee
    Senior Principal Scientist
    Novartis
    Harleysville PA
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message