Transcript Dr. Phil Rowe Reader in Pharmaceutical Computing

ADME lecture 5
Contents ...
• Constant i.v. infusion
• Multiple dosing
Part 1
Constant i.v. infusion
Constant i.v. infusion
Drug in solution
in sterile saline
Constant
rate infusion
pump
Flexible plastic catheter
inserted into a vein
Constant i.v. infusion
Input (Rinf)
Is fixed
Rate of change in Ab
Depends upon balance
between Input & Output
V
Output
Varies with
body load
i.v. Infusion
Elim = Rinf
Css
Elim < Rinf
Elim << Rinf
Predicting Css
Css =
Rinf
Clearance
This equation is general i.e. it is not
restricted to one compartment
models.
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
Need for a loading dose
No effective treatment for (approx) first 4 hours
Use of a loading dose
Immediately effective treatment
With loading dose
No loading dose
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
Part
Multiple dosing
Accumulation
Much of previous dose still present
Previous dose almost fully eliminated
“Steady state”
Amount
eliminated
<< 1 dose
Amount
eliminated
< 1 dose
Amount
eliminated
= 1 dose
Concentrations at
Steady State
Css,max = “Peak”
Css
(Average)
Css,min = “Trough”
Predicting Css
Fractional
bioavailability
Individual
dose size
Css = F . D
Cl . 
Clearance
Dosage
interval
e.g. If doses given twice daily,  = 12 hours.
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
Cl.
rearranges to:
D = 0.8 mMole/L x 1.5 L/h x 24 h
1.0
= 28.8 mMole
D = Css.Cl.
F
Terms with which you
should be familiar ...
Infusion
Steady state
Loading dose
Accumulation
Css (Pronounced “C bar SS”)
Css,max
Css,min
Dosage interval ()
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).