1 chapter 4 intravenous infusion. 2 one compartment model with iv infusion this can be obtained by...
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CHAPTER 4
INTRAVENOUS INFUSION
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ONE COMPARTMENT MODEL WITH IV INFUSION
This can be obtained by high degree of precision by infusing drugs i.v. via a drip or pump in hospitals
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PK of Drug Given by IV Infusion
Zero-order Input (infusion rate, R)
First-order Output (elimination)
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Integrated equationZero-order Input (infusion rate, R)
First-order Output (elimination)
By integration,
pelp CkR
dt
dC
)1( tk
eldp
elekV
RC
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Stopping the Infusion Stopping the infusion before reaching steady state
Infusion stops
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Stopping the Infusion Equations
tkpp
eleCC 0
)1( tk
eldp
elekV
RC
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Steady State ConcentrationIV Infusion until reaching Css
Cl
RCss
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Steady State Concentration (Css)
Theoretical SS is only reached after an infinite infusion time
Rate of elimination = kel Cp
)1( ekV
RC
eldp
Cl
R
kV
RC
eldss
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Steady State Concentration (Css)
Rate of Infusion = Rate of Elimination
The infusion rate (R) is fixed while the
rate of elimination steadily increases
The time to reach SS is directly
proportional to the half-life
After one half-life, the Cp is 50% of the CSS, after 2 half-lives, Cp is 75% of the
Css .……
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Steady State Concentration (Css)
In clinical practice, the SS is considered to be reached after five half-lives
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Increasing the Infusion Rate If a drug is given at a more rapid infusion rate, a higher SS drug concentration is obtained but the time to reach SS is the same.
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Loading Dose plus IV Infusion DL with IV infusion at the same time
)1( tk
eld
tk
d
Lp
elel ekV
Re
V
DC
tk
d
Ltkp
elel eV
DeCC
1
)1(2tk
eld
elekV
RC
Loading dose
IV infusion
DL + IV infusion
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Loading Dose plus IV Infusion
DL is used to reach SS rapidly
)1( tk
eld
tk
d
Lp
elel ekV
Re
V
DC
tk
eldeld
tk
d
Lp
elel ekV
R
kV
Re
V
DC
tk
eld
tk
d
L
eldp
elel ekV
Re
V
D
kV
RC
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Reaching SS Immediately
Let , DL = CssVd But, CssVd = R / kel
Therefore, if a DL = R / kel is given SS will be reached immediately
tk
eld
tk
d
L
eldp
elel ekV
Re
V
D
kV
RC
eldp kV
RC
eldss kV
RC but
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Reaching SS Immediately IV DL equal to R /kel is given, followed by IV infusion at a rate R
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DL + IV Infusion