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PBPK Model

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.

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53 views14 pages

PBPK Model

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.

Uploaded by

varish
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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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.

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