Scribd Logo
Upload

Welcome to Scribd!

  • 32 views

    PBPK Model

    Uploaded by

    varish
    This document discusses physiology-based pharmacokinetic (PBPK) models. PBPK models combine information about a drug with knowledge of organism physiology to simulate drug concentration over time in different organs and tissues. This allows estimation of drug exposure at sites of action. A PBPK model contains representations of important organs like liver and kidney. Parameters include organ properties, drug properties, and administration details. Commercial software packages can be used to build PBPK models using integrated physiological and compound data.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd

    PBPK Model

    Uploaded by

    varish
    32 views14 pages
    This document discusses physiology-based pharmacokinetic (PBPK) models. PBPK models combine information about a drug with knowledge of organism physiology to simulate drug concentration over time in different organs and tissues. This allows estimation of drug exposure at sites of action. A PBPK model contains representations of important organs like liver and kidney. Parameters include organ properties, drug properties, and administration details. Commercial software packages can be used to build PBPK models using integrated physiological and compound data.

    Original Title

    PBPK_model

    Copyright

    © © All Rights Reserved

    Available Formats

    PPTX, PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    This document discusses physiology-based pharmacokinetic (PBPK) models. PBPK models combine information about a drug with knowledge of organism physiology to simulate drug concentration over time in different organs and tissues. This allows estimation of drug exposure at sites of action. A PBPK model contains representations of important organs like liver and kidney. Parameters include organ properties, drug properties, and administration details. Commercial software packages can be used to build PBPK models using integrated physiological and compound data.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    32 views14 pages

    PBPK Model

    Uploaded by

    varish
    This document discusses physiology-based pharmacokinetic (PBPK) models. PBPK models combine information about a drug with knowledge of organism physiology to simulate drug concentration over time in different organs and tissues. This allows estimation of drug exposure at sites of action. A PBPK model contains representations of important organs like liver and kidney. Parameters include organ properties, drug properties, and administration details. Commercial software packages can be used to build PBPK models using integrated physiological and compound data.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 14

    Physiology

    based
    PK Model
    Surulivelrajan M
    Associate Professor,
    Department of Pharmacy Practice,
    MCOPS, MAHE
    Introduction
    • PBPK models combine information on the drug with
    independent prior knowledge on the physiology and biology
    at the organism level to achieve a mechanistic
    representation of the drug in biological systems, allowing the
    a priori simulation of drug concentration–time profiles.
    PBPK Model…
    • Since PBPK models explicitly consider different organs and tissues, it is
    possible to obtain the quantitative characterization of concentration–
    time profiles in the respective compartments.

    • PBPK enables the estimation of drug exposure not only in plasma but
    also at the site of action, which may be difficult or impossible to
    measure experimentally.
    PBPK Model…

    • A whole-body PBPK model contains an explicit representation of the


    organs that are most relevant to the absorption, distribution,
    excretion, and metabolism of the drug due to their
    physiological/pharmacological function or their volume.
    PBPK Model…
    • These are typically heart, lung, brain, stomach, spleen, pancreas, gut,
    liver, kidney, gonads, thymus, adipose tissue, muscle, bone, and skin.

    • The tissues are linked by the arterial and venous blood


    compartments, and each one of them is characterized by an
    associated blood-flow rate, volume, tissue-partition coefficient, and
    permeability.
    PBPK Model…
    • A major advantage of PBPK modeling is the availability of a
    comprehensive structural representation of the physiology of an
    organism.
    • The various parameters in the model are either obtained from
    compilations of prior knowledge or may be calculated from specific
    and carefully validated formulas.
    • From a general point of view, it is possible to distinguish between
    organism parameters on the one hand and drug parameters on the
    other
    Hierarchical relationship of parameters in a
    PBPK model
    Organism Properties - special cases
    • Organism properties are, for instance, organ volumes, organ
    composition, blood flows, surface areas, and expression levels.

    • Such properties are dependent on the species or population


    considered.

    • For example, in the case of special populations (e.g., diseased or


    pediatric populations) these organism properties take into account
    physiological differences between the special populations and the
    healthy adult reference population
    Drug Properties
    • Drug properties include all parameters specific for the compounds
    under study. Notably, physicochemical properties such as compound
    lipophilicity, solubility, molecular weight (MW), and pKa values of a
    drug are fully independent of organism physiology.

    • Drug-biological properties (such as fraction of drug unbound, or


    tissue-plasma partition coefficient), on the other hand, are drug-
    specific but also defined by the interaction between the drug and the
    biological system itself, so they are dependent on both the drug and
    the organism properties.
    • Finally, information on the administration protocol and formulation
    properties is needed to define a PBPK simulation.

    • Time-related special events such as gallbladder emptying time or


    meal intake can also be included in the model and their impact on
    drug PK can be evaluated with the model.
    Softwares used for PBPK model

    • GastroPlus (Simulations Plus, Lancaster, PA),


    • SimCyp (SimCyp, Sheffield,UK),
    • PK-Sim and MoBi (Bayer Technology Services,Leverkusen, Germany).
    • These commercial PBPK modeling platforms provide a generic model
    structure for the physiology of predefined species and populations.

    • They all include physiological databases that are combined with


    compound-specific information as well as biometric data, and are
    used to parametrize a PBPK model on a whole-body level.

    You might also like