Download - Pk lab 5
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Biopharmaceutics and PK
Lab 5Calculation of PK parameters using one and two compartment model: IV
bolus.
Dr Sameh Rabea
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Remember
For 1st order kinetic one-compartment the equation will be:
Cp= (Cp) 0 e –kt Where: Cp: Y ; (Cp) 0 : intercept; t: X; k: -slope x
2.303; Slope= (logC2 – logC1)/t2-t1.
Or Ke = ln (C1/C2)/t2-t1
The PK model:
Ke
Out.
AUC= Cp0/ Ke
Vdc= Dose/ Cp0.
t ½= 0.693/ Ke.
I.V. injection
Central Compartment
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For 1storder kinetic two-compartment the equation will be:
Cp= A e –αt + B e –βt
Where A: intercept of line 1 and B intercept of line 2; α: distribution rate constant and β: elimination rate constant.
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The PK model:
in K12
K 21
K2
Cp0= A + B
K2 = Cp0 / ( A/ α + B/ β )
K12= A.B (β- α) 2 / Cp0 (A β + B α)
K21= A β + B α / Cp0 .
I.V. inj.
Central Compartment
Peripheral Compartment
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AUC= A/α + B/β . t ½= 0.693/ β.
Vd c= Dose/Cp0= Dose/ A+B.
Vd area= Dose/AUC. β
Vd ss = Vdc + (K12/K21) Vdc
Vd tissue= Vd area – Vdc.
Therefore: Vd area> Vd ss > Vdc> Vd tissue.
But Vd ss is not affected by elimination, so its represents true volume of distribution.
CL = Vdc. Ke or CL= Vdc. Β.
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Problem # 1
A patient received 500 mg cefepime I.V bolus injection and numerous blood samples were drawn as the following:
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Plotting Data
Time (hr) µ/ml) Conc(.
0.5 38.2
1 21.6
2 11.6
4 5.0
8 1.4
12 0.2
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A- Test the order of this data. B- Write your model Calculate as many PK parameter as
possible.
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Problem # 2
A patient received 300 mg I.V. dose of a drug. Several blood samples were collected and the following plasma concentrations were obtained:
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Plotting Data
µ/ml) Conc(. Time (hr)
5.6 0.2
4.6 0.4
3.8 0.6
3.2 0.8
2.8 1
1.8 2
1.35 3
1.2 4
1.06 5
0.0 24
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Test the order of this data. Write the model. Calculate PK parameters.
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Problem # 3
A patient received 350 mg I.V bolus dose of drug. Several blood samples were collected and the following plasma concentrations were obtained:
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Plotting Data
Time (hr) Conc. (µg/ml)
0.5 20.8
1 13.8
1.5 10
2 7.9
3 5.3
6 2.9
8 2
10 1.4
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A- Draw diagrammatic presentation describing PK model , and write your equation.
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Calculate the following PK parameters: A: B: α: β (Ke): t1/2 : AUC: Vdc:
Vd area: