Pharmacokinetic models are used to understand and describe the movement of drugs in the body mathematically. There are two main approaches: compartment models which divide the body into compartments and use rate constants to describe drug transfer, and non-compartmental models which do not assume a compartment structure and describe kinetics using time and concentration parameters. Common compartment models include one, two, and three compartment mammillary models as well as perfusion-limited and diffusion-limited physiological models. Both approaches have advantages and limitations in analyzing pharmacokinetic data.

1. Pharmacokinetics Models
Dr. Nilesh S. Kulkarni
PES Modern college of Pharmacy (For Ladies)
Moshi Pune

2. Need Of Pharmacokinetic Models
• Drug movement within the body is a complex process.
• To understand the movement of drug in biological system
pharmacokinetic models come under consideration.
• For ease of mathematical equation understanding
pharmacokinetic models are required.
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3. Pharmacokinetic Models
• Model is a hypothetical space bound by an unspecified
membrane across which drugs are transferred in and out.
• Model is a hypothesis that employs mathematical terms to
concisely describe quantitative relationships.
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4. Methods For Analysis Of Pharmacokinetic Data
• The two major approaches in the quantitative study of
various kinetic process of drug disposition in body are
1. Model approach
2. Model-independent approach
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5. Model Approach
• In this approach, models are used to describe changes in drug
concentration in the body with time.
1 Compartment Model (empirical model)
(a) Mammillary Model
(b) Catenary Model
2 Physiological Model
(a) Perfusion-Limited Model (b) Diffusion-Limited Model
3 Distributed Parameter Model
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6. Mammillary model
• Arrangement of compartments in a manner similar to
connection of satellites to a planet
• Central compartment (compartment 1)
• Plasma
• Highly perfused tissues (such as lung, liver
kidney)
• Peripheral compartment (denoted by no. 2,3, etc)
• Other organs
• Elimination occurs from central compartment
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7. Mammillary model continuous…
• Movement of drug between compartments is defined by
characteristic first order rate constant denoted by later K.
• The number of rate constant in a particular compartment
model is given by R.
For IV administration R= 2n-1
For extravascular administration R=2n
n= number of compartment
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8. Model 1 One-compartment open model, intravenous
bolus administration.
Model 2 One-compartment open model, extravascular
administration.
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1
K10
1
K10K01

9. Model 3 Two-compartment open model , intravenous
bolus administration.
Model 4 Two-compartment open model , extravascular
administration.
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1 2
K12
K10
1 2
K12
K10
K01
K 21

10. Model 5 Three-compartment open model, intravenous
administration.
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2
31
K21K12
K13
K31
K10

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2
31
K21
K21
K13
K31
K10
K01
Model 5 Three-compartment open model, extravascular
administration.

12. Catenary Model
• In this model compartments are joined to one another in a
series.
• This model is rarely used.
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1
2 3
K01 K12
K21
K23
K32

13. ADVANTAGES OF COMPARTMENT
MODELING
• It is a simple and flexible approach.
• It gives a visual representation of various rate processes
involved in drug disposition.
• It is important in development of dose regimens.
• Used for comparison of multiple therapeutic agents.
• It show how many rate constant required for describing
these process.
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14. DISADVANTAGES OF COMPARTMENT
MODEL
• The compartment and parameters have no relationship with
physiological functions or anatomical structure of the
species.
• Model may vary within population pharmacokinetics.
• This approach is limited to specific drug only.
• Difficulties generally arises when using model to interpret
the differences between results from human and animal
experiments.
• The model is based on curve fitting of plasma
concentration with complex multi-exponential
mathematical equations.
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15. Physiological Model
• Also know as physiologically-based pharmacokinetic
models (PB-PK models).
• It describe the drug disposition in terms of realistic
physiological parameters.
• Number of compartments in the model depends upon
the disposition characteristics of drug.
• Organs such as bone that have no drug penetration are
excluded.
• RET (rapidly equilibrating tissue)- lungs, liver, brain, and
kidney.
• SET (slowly equilibrating tissue)- muscles and adipose tisse.
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16. LUNG
HEART
GUT LIVER
LIVLIVE
R
KIDNEY
HPT
PPT
VENOUSBLOOD
ARTERISLBLOOD
QLung
QL-QG
QG
QL
QK
QHPT
QPPT
I.V. DOSE
KM
Ke
elimination
elimination

17. Physiological Model Continuous…
The rate of drug carried to a tissue/organ or tissue drug uptake is
dependent upon two major factors
• Rate of blood flow to the organ
• Tissue/Blood partition coefficient or diffusion coefficient of drug
On this basis physiological model are two type-
Blood flow rate limited models (Perfusion rate-limited model)
Membrane permeation rate limited models (Diffusion-limited model)
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18. Perfusion rate-limited model
• This model is based on the assumption that the drug movement
within a body region is much more rapid than its rate of delivery to
that region by the per fusing blood.
• Applicable only for highly membrane permeable drug(s) i.e. low
molecular weight, poorly-Ionized, and high lipophilic drugs.
thiopental, lidocaine
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19. Diffusion-limited model
• Model is applicable for highly polar, ionized drugs for
which cell membrane act as a barrier and gradually
permeates it by diffusion.
• Equation for these models are very complicated.
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20. Advantages Of Physiological Modeling
• Mathematical treatment is straightforward.
• The model is suitable where tissue drug concentration and
binding are know.
• Data fitting is not required.
• Exact description of drug concentration-time profile in any
organ or tissue can be obtained.
• The influence of altered physiology or pathology on drug
disposition can be easily predicted from changes in various
pharmacokinetic parameter.
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21. Disadvantages Of Physiological Modeling
• Obtaining experimental data, which is very exhaustive.
• Prediction of individualized dosing is difficult.
• Number of data point is less than the pharmacokinetic
parameters to be assessed.
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22. Distributed Parameter Model
• Analogous to physiological model.
• Designed only for determining Variation in blood flow to
an organ, Variation in drug diffusion in an organ.
• Specifically used for assessing regional differences in
drug concentration in tumors or necrotic tissue.
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24. NON-COMPARTMENTAL MODEL
• Also know as model-independent-method.
• Based on the assumption that the drugs or metabolites follow
linear kinetics.
• It dose not require the assumption of specific compartment
model.
• Applicable to any compartment model.
• Describe the pharmacokinetics of drug disposition using time
and concentration parameters.
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NON-COMPARTMENTAL MODEL

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27. Advantages Of Non-compartmental Model
• Pharmacokinetic parameters can be easily derived.
• A detailed description of drug disposition is not required.
• Applicable for any drug or metabolite which follow first-
order kinetics.
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28. Disadvantages Of Non-compartmental Model
• Provide limited information regarding the plasma drug
concentration-time profile.
• This method does not adequately treat non-linear cases.
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