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Modeling in Pharmacokinetics

The document discusses models used to understand how organisms interact with chemicals and drugs. It describes compartmental and noncompartmental modeling approaches. Compartmental models use differential equations to model concentrations over time, while noncompartmental methods directly analyze concentration-time measurements. Both approaches aim to understand exposure and characterize parameters like maximum concentration. The most accurate models still involve simplifying assumptions and do not perfectly reflect reality.

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vijay kumar honnali
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39 views1 page

Modeling in Pharmacokinetics

The document discusses models used to understand how organisms interact with chemicals and drugs. It describes compartmental and noncompartmental modeling approaches. Compartmental models use differential equations to model concentrations over time, while noncompartmental methods directly analyze concentration-time measurements. Both approaches aim to understand exposure and characterize parameters like maximum concentration. The most accurate models still involve simplifying assumptions and do not perfectly reflect reality.

Uploaded by

vijay kumar honnali
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as DOCX, PDF, TXT or read online on Scribd
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Modeling[edit]

Models have been developed to simplify conceptualization of the many processes that take place in
the interaction between an organism and a chemical substance. Pharmacokinetic modelling may be
performed either by noncompartmental or compartmental methods. Multi-compartment
models provide the best approximations to reality; however, the complexity involved in adding
parameters with that modelling approach means that monocompartmental models and above all two
compartmental models are the most-frequently used. The model outputs for a drug can be used in
industry (for example, in calculating bioequivalence when designing generic drugs) or in the clinical
application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance
guidelines for effective and efficient use of drugs for human-health professionals and in veterinary
medicine.

Models generally take the form of mathematical formulas that have a corresponding graphical
representation. The use of these models allows an understanding of the characteristics of
a molecule, as well as how a particular drug will behave given information regarding some of its
basic characteristics such as its acid dissociation constant (pKa), bioavailability and solubility,
absorption capacity and distribution in the organism. A variety of analysis techniques may be used to
develop models, such as nonlinear regression or curve stripping.

Noncompartmental analysis[edit]
Noncompartmental methods estimate PK parameters directly from a table of concentration-time
measurements. Noncompartmental methods are versatile in that they do not assume any specific
model and generally produce accurate results acceptable for bioequivalence studies. Total drug
exposure is most often estimated by area under the curve (AUC) methods, with the trapezoidal
rule (numerical integration) the most common method. Due to the dependence on the length of x in
the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling
schedule. That is, the closer time points are, the closer the trapezoids reflect the actual shape of the
concentration-time curve. The number of time points available in order to perform a successful NCA
analysis should be enough to cover the absorption, distribution and elimination phase to accurately
characterize the drug. Beyond AUC exposure measures, parameters such as Cmax (maximum
concentration), Tmax (time to maximum concentration), CL and Vd can also be reported using NCA
methods.

Compartmental analysis[edit]
Compartment models methods estimate the concentration-time graph by modeling it as a system of
differential equations. These models are based on a consideration of an organism as a number of
related compartments. Both single compartment and multi-compartment models are in use. PK
compartmental models are often similar to kinetic models used in other scientific disciplines such
as chemical kinetics and thermodynamics. The advantage of compartmental over noncompartmental
analysis is the ability to modify parameters and to extrapolate to novel situations. The disadvantage
is the difficulty in developing and validating the proper model. Although compartment models have
the potential to realistically model the situation within an organism, models inevitably make
simplifying assumptions and will not be applicable in all situations. However complicated and precise
a model may be, it still does not truly represent reality despite the effort involved in obtaining various
distribution values for a drug. This is because the concept of distribution volume is a relative concept
that is not a true reflection of reality. The choice of model therefore comes down to deciding which
one offers the lowest margin of error for the drug involved.

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