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A SEMINAR ON ONE & TWO COMPARTMENT OPEN MODEL
EXTRA VASCULAR ADMINISTRATION
PRESENTED BY SANKAR DASARI
M PHARM ,PHCETS ,1 YR 2 SEMMALLAREDDY COLLEGE OF PHARMACY
GUIDED BY Dr. SATYA BRATA BHANJA sir
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Pharmacokinetic models are used to simplify all the processes that occur during drug administration that include drug distribution and elimination in the body.
Compartment models – Classical pharmacokinetic modelsThat stimulate the kinetic processes of drug A,D and E
Compartment models broadly categorised into two typesSingle compartment model One compartment model Multiple compartment model which includes Two compartment model Three compartment model
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One Compartment Open model extra vascular administration can be shown
in a diagrammatic way by the following diagram
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Normal and semi log plots depicting one compartment open model extra vascular administration
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In One Compartment open model EXTRAVASCULAR ADMINISTRATIONWhen drug is administered by extravascular route, absorption is prerequisite for its therapeutic activity. The rate of absorption may be described mathematically as zero-order or first-order process.After e.v. administration, the rate of change in the amount of drug in the body is given by
dx = Rate of absorption – Rate of elimination dt
dX = dXev - dxe dt dt dt
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• During absorption phase, the rate of absorption is greater than elimination phase.
dXev > dxe dt dt
• At peak plasma concentration,
dXev = dxe dt dt
• During post absorption phase,
dXev < dxe dt dt
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ZERO-ORDER ABSORPTION MODEL R0 KE
Drug Blood Excretion
This model similar to that of constant rate infusion and all equation which applies to it are applicable to this model.
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FIRST-ORDER ABSORPTION MODEL Ka KE
Drug Blood Excretion first order
From equ. dX = dXev - dxe dt dt dtDifferentiating above equ. We get, dX = Ka Xa – KEX, Ka= absorption rate const. dt Xa= amt of drug remaining to be absorbed.Integrating above equ.,
X =
[ ]tKTK
Ea
oa aE eeKK
FXK −− −− )(
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ABSORPTION RATE CONSTANT This can be calculated by METHOD OF RESIDUALS. Method is also known as Feathering, stripping and peeling. Drug that folllows one- compartment kinetics and administered e.v. , the concentration of drug in plasma is expressed by biexponential equation:
Assuming A = Log Ka F X 0 Vd (Ka – KE) C = A e-kEt – A e-Kat
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During the elimination phase, when absorption is most over, Ka >>KE
C = A e-Ket In log form above equation is Log C = Log A - Ket
2.303 Where, C = back extraplotted plasma conc. Values.Substracting true plasma conc. From extraploted one,
log(C – C ) =Cδ = Log A - Ket 2.303
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This method works best when difference between Ka KE is large (Ka/KE >3)
If KE/Ka > 3 , the terminal slope estimates Ka and not KE whereas the slope of residuals line gives Ke and not Ka.
This is called as flip-flop phenomenon since the slopes of the two lines have exchanged their meanings.
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Wagner Nelson Method for Estimation of Ka The method involves determination of ka from percent un absorbed- time plots and does not required assumption of zero or first- order absorption
After oral administration of single dose of drug at any given time ,the amount of drug in the body X and the amount of drug eliminated from the body XE .Thus:
X=VdC ,
The total amount of drug absorbed into systemic circulation from time zero to infinite can be given as :
Since at t = ∞, ,the above equation reduce to :
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The fraction of drug absorbed at any time t is given as:
Percent drug unabsorbed at any time is therefore:
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Two compartment open model extra vascular administration
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References:1.D.M. Brahmankar, compartment model in Biopharmaceutics and Pharmacokinetics, Vallabh prakashan, second editon, 2009; p:2.Applied Biopharmaceutics and Pharmaceutics sixth edition LEON SHARGEL