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COMPARTMENTAL & NON-COMPARTMENTAL

PHARMACOKINETICS

REVIEW OF TERMINOLOGY
INTRODUCTION TO PHARMACOKINETICS

Pharmacokinetics is defined as the Kinetics of drug


absorption, distribution, metabolism, and excretion and
their relationship with pharmacological, therapeutic or
toxicological response in human and animals.

The applications of pharmacokinetic principles in safe


and effective management of individual patient is
called as clinical pharmacokinetics.
PEAK PLASMA CONCENTRATION-TIME
PROFILE
A direct relationship exists between the concentration of
drug at the biophase (site of action) and the concentration
of drug in plasma.
With Single Dose Study, the method requires collection of
serial blood samples for periods of 2 to 3 biological half-lives
after drug administration, their analysis for drug concentration
and making plot of concentration versus corresponding time
of sample collection to obtain the plasma level-time profile.
A PLASMA DRUG CONCENTRATION-TIME
PROFILE AFTER ORAL ADMINISTRATION OF
SINGLE DOSE OF DRUG
KEY PARAMETERS

Pharmacokinetic parameters:
 Peak plasma concentration (Cmax)
• Peak time (tmax)
• Area under curve (AUC)

Pharmacodynemic Parameters :
 Minimum effective concentration
 Maximum safe concentration
 Onset of action
 duration of action
 Therapeutic range and therapeutic Index
PHARMACOKINETIC PARAMETERS
PEAK PLASMA CONCENTRATION:
The maximum conc. of drug in plasma observed after
administration of dosage form is called peak plasma
concentration.
PEAK TIME:
The time for drug to reach peak conc. in plasma is called time of
peak concentration.
AREA UNDER CURVE:
It represents total integrated area under the plasma level-time
profile and express the total amount of drug that comes into
systemic circulation after its administration.
PHARMACODYNAMIC PARAMETERS
MINIMUM EFFECTIVE CONC.(MEC):
It is defined as minimum conc. Of drug in plasma required to produce therapeutic
effect .The conc. Of drug below MEC is said to be in subtherapeutic level.

MAXIMUM SAFE CONC. :


Also called as MINIMUM TOXIC CONC.(MTC).
It is the conc. Of drug in plasma above which adverse effects are precipitated.
Conc. Of drug above MSC is said to be in toxic level.

ONSET OF ACTION:
The beginning of pharmacologic response is called as onset of action.

DURATION OF ACTION:
The time period for which plasma conc. Of drug remains above MEC is called
duration of action.

THERAPEUTIC RANGE:
The drug conc. Between MEC and MSC represents therapeutic range.
FRACTION OF DRUG ABSORBED

 It is the ratio of amount of drug ultimately reaching


the blood stream to the total drug administered.
 Value of F will be unity if total administered dose
reaches the blood circulation.
 Many dosage form show F value less than unity
because of
1. slow release of drug from dosage form
2. degradation of durg in GIT due to chemical or
enzymatic processes.
3.drug undergoes first pass effect.
THE SIGNIFICANCE OF MEASURING PLASMA
DRUG CONCENTRATIONS

The intensity of pharmacological & toxic effect of a drug is often


related to the Concentration of the drug at the receptor site usually
located in the tissue cells.
Because most of the tissue cells are richly perfused with tissue
fluids or plasma.
Monitoring of plasma drug concentration allows for the
adjustment of the drug dosage in order to individualize & optimize
therapeutic drug regimens.
It helps in determining therapeutic equivalents & therapeutic
substitutions.
PHARMACOKINETIC MODELS
PHARMACOKINETIC MODELS

 It provides the concise means of expressing


mathematically or quantitatively, time course of
drug through out the body and compute
meaningful p’cokinetic parameters
COMPARTMENTAL MODEL

 Hypothetical space bound by an unspecified


membrane across which drugs are transferred in and
out.

 Depending upon whether the compartments are


arranged parallel or in a series classified as :
 Mammillary model
 Caternary model.
MAMMILLARY MODEL

 Arrangement of one or more peripheral compartments to


central compartment in a manner similar to connection
of satellites to a planet (i.e. they are joined parallel to
central comptt.)

 Central compartment comprises of plasma and highly


perfused tissues such as lungs,liver,kidney, etc.

 Peripheral compartment contains other organs with


low vascularity and poor perfusion.

 Elimination occurs from central compartment


O

Model 1 One compartment open model,


intravenous bolus administration

K 10
1

Model 2 One compartment open model,


extravascular administration

K01 1 K10
 Model 3 Two compartment open model,
intravenous bolus administration

K12
2
1
K21

K10
I
 Model 4 Two compartment open model,
extravascular administration

K12
K01 1 2

K21

K10
I
CATERNARY MODEL

In this model, the compartments are joined to one another in a


series

K12 K23
2 3
K01 1
K21 K32
 model independent method
 Describe the pharmacokinetics of drug disposition using time
and concentration parameters.
 Method can however be applied to any compartment model
provided the drugs or metabolites follow linear kinetics.
 The approach based on statistical moments theory.
 If one considers the time course of drug concentration in
plasma as a statistical distribution curve, then:
MRT = AUMC
AUC
Where MRT= mean residence time
AUMC=area under first-moment curve
AUC=area under zero-moment curve
PHYSIOLOGICAL MODEL

 Called as physiologically based pharmacokinetic model.


 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
 divided in two types –
Blood flow rate limited models
Membrane permiatiation rate limited models
ANY QUERY !!!!