ADME lecture 5 Contents '''

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ADME lecture 5Contents ...

• Constant i.v. infusion
• Multiple dosing

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Part 1
Constant i.v. infusion
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Constant i.v. infusion
Drug in solution in sterile saline
Constant rate infusion pump
Flexible plastic catheter inserted into a vein
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Constant i.v. infusion
Input (Rinf) Is fixed
Rate of change in Ab Depends upon balance between
Input Output
V
OutputVaries with body load
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i.v. Infusion
Elim Rinf
Css
Elim lt Rinf
Elim ltlt Rinf
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Predicting Css
Css Rinf Clearance
This equation is general i.e. it is not
restricted to one compartment models.
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Calculating infusion rate
We want to achieve a Css of 15 mg/L. Clearance
3 Litre/h Css Rinf / Cl Rinf Css x Cl
15 mg/L x 3 Litre/h 45 mg/h
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Need for a loading dose
No effective treatment for (approx) first 4 hours
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Use of a loading dose
Immediately effective treatment
With loading dose
No loading dose
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Calculating loading dose
Concentration achieved Loading dose
Vol Dis
C LD
V
LD C x V
(LD is given i.v., so no need to consider F)

• Target conc 15 mg/L
• Vol dis 50 Litres
• LD 15 mg/L x 50 L
• 750 mg

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Part
Multiple dosing
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Accumulation
Much of previous dose still present
Previous dose almost fully eliminated
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Steady state
Amount eliminated 1 dose
Amount eliminated ltlt 1 dose
Amount eliminated lt 1 dose
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Concentrations at Steady State
Css,max Peak
Css (Average)
Css,min Trough
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Predicting Css
Fractional bioavailability
Individual dose size
Css F . D Cl . ?
Clearance Dosage
interval
e.g. If doses given twice daily, ? 12 hours.
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Example calculation
What daily dose of Lithium to achieve Css of 0.8
mMole/L, given that F 100
Cl 1.5 L/h Css F.D
rearranges to D Css.Cl.?
Cl.?
F D 0.8 mMole/L x 1.5 L/h
x 24 h 1.0
28.8 mMole
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Terms with which you should be familiar ...
Infusion Steady state Loading dose Accumulation
Css (Pronounced C bar SS) Css,max
Css,min Dosage interval (?)
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What you should be able to do

• Describe why the graph of concentration versus
  time of infusion adopts its distinctive shape.
• Calculate a rate of infusion from intended Css
  and clearance (etc).
• Describe the purpose of a Loading Dose
• Calculate an appropriate LD from Css V
• Describe accumulation and explain why a steady
  state is eventually achieved.
• Predict Css from F, D Cl and ? (etc).