Pharmacokinetics of Controlled drug delivery sysytem

1. Prepared By:- Dheeraj Kumar
M.S.(Pharmaceutics)
443/MS-PE/17
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2. Contents
 Introduction
 Absorption
 Distribution
 Metabolism
 Excretion
 Pharmacokinetic Prameters
 Pharmacokinetic models
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3. PHARMACOKINETICS
 Kinetics of drug absorption, distribution, metabolism
and excretion (KADME) and their relationship with
pharmacological and therapeutical response.
 Pharmacokinetics = pharmackon + kinetikos
(drug) (moving)
 Stduy of movement of drug inside the body.
 Pharmacokinetics is what body does to the drug.
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4. Cont…
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5. Cont…
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6. Absorption
 Ideal CRDDS should release the complete drug and
the released drug should be completely absorbed
 The fraction of drug absorbed from the system can be
lower than the expected due to:
-degradation of drug. Eg- Penicillin G
-site-specific, dose-dependent absorption,
-poor water solubility
-small partition coefficient.
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7. Distribution
 Distribution refers to the reversible transfer of drug
from one location to another inside the body.
 Depends on affinity of drug to bind with plasma
proteins and ability of drug to pass through tissue
membranes.
 Apparent volume of distribution (Vd) is defined as the
hypothetical volume of body fluids to which a drug is
dissolved or distributed.
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8. Metabolism
 Metabolism of a drug is either an inactivation, of an active
drug or conversion of an inactive drug to an active
metabolite or active drug with active metabolites. There are
two factors related to metabolism of drug which restrict
the design of CRDDS:
 Drugs possessing variations in bioavailability due to first-pass
effect or intestinal metabolism are not suitable for
sustained/controlled drug delivery.
 For chronic administration, drugs that are capable of either
inducing or inhibiting enzyme synthesis, are poor candidates
for controlled delivery systems due to difficulty in
maintaining uniform blood levels.
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9. Elimination
 Ir-reversible removal of drug from the body.
 Time taken for the amount of drug in body by one half
is called elimination half life.
 The loss of drug across an organ is viewed as
clearance.
 Clearnce can be presented in terms of eliminating
oragn such as hepatic clearance, renal clearance etc.
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10. Pharmacokinetics Parameters
 Elimination half life
 Protein binding of drug
 Apparent volume of distribution(Vd)
 Cmax
 Tmax
 Area under the concentration time curve(AUC)
 Clearance
 Absolute Bioavailability
 Relative Bioavailability
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11. Cont…
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12.  Elimination half life:
 It is the time required to reduce the concentration in
plasma to one half of the initial concentration.
 Independent of the amount of drug in the body.
 Depends on Clearnce and Volumne of distribution.
 The shorter the half life greater will be the amount of
drug to be incorporated in the delivery system.
 Drugs with t1/2 of 3-4 hours are best candidate for
controlled drug delivery system.
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13. Cont…
Half life determination
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14. Protein Binding of Drug
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15.  Apparent volume of distribution(Vd)
 Hypothetical volume of body fluids into which a drug
is distributed
Vd=X/C
Where
X=Amount of drug in body
C=Plasma drug concentartion
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16.  Drugs which binds to plasma proteins have low Vd while
the drugs which binds to extravascular tissues have high
Vd.
 For Example:- Warfarin(10 liters) , Chloroquin(15000
liters)
Fluids compartments of an adult
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17.  Area under the concentration time curve(AUC):
 AUC is the measure of quantity of drug in the
body.
 AUC is generally determined by trapezoidal rule.
 Absolute bioavailability and relative bioavailability
are caluculated from AUC.
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18.  Absolute Bioavailability:-
 compares the bioavailability of the active drug
following extravascular administration with the
bioavailability of the same drug following
intravenous administration
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19.  Relative Bioavailability:-
 A type of comparative bioavailability
assessment
 Relative bioavailability studies compare two
drug product formulations
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20.  Clearance :
 Clearance is the hypothetical volume of body fluids
containing drug from which the drug is cleared
completely in a specific period of time.
 It is expressed in ml/min or litre/hour.
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21.  Mean residence time:
 It is the mean time a drug molecule reside in the
body
 It is calculated from AUC and AUMC
MRT = AUMC/AUC
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22. Pharmacokinetic models
 A model is a hypothesis that employs mathematical
terms to concisely describe quantitative relationships.
 Used for determination for various pharmacokinetic
parameters
 A pharmacokinetic function relates an independent
variable to a dependent variable.
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23. Pharmacokinetic
models
Compartmental
models
Catenary models
Mammillary
models
Physiological
models
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24. Catenary model
 Various compartments are joined to each other in
series like the compartments of train.
 This model is rarely used.
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25. Mammillary model
 Most common model used in pharmacokinetics.
 One or more peripheral compartments connected to
central compartment.
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26. Physiological model
 Pharmacokinetic models based on known anatomic
and physiologic data.
 The model would potentially predict realistic tissue
drugconcentrations, which the two-compartment
model fails to do.
 Unfortunately, much of the information required for
adequately describing a physiologic pharmacokinetic
model are experimentally difficult to obtain.
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27. THANK YOU
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