Dear Samer and Simon,
I would like to further discuss some points from my previous questions:
1 / weighting:
I understand that to get 1 / Y * Y or 1 / Yhat * Yhat like in a classic WinNonLin model, a multiplicative error model must be used. By this way, I obtained an error model as followed
error(CEps = 1)
observe(CObs = C * (1 + CEps))
which I assumed to be equivalent to 1 / Y * Y
Previously, you said that for predicted values, (Cpred + Cpred*eps) for 1 / Yhat * Yhat must be the error model used. But I did not manage to implement it correctly. Could you please write all of the 2 lines with this weighting?
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try experimenting with the different error options to see how to write in pm;
it is not advised to use the observations as weights ( Y ) but use Y hat or PRED
observe(CObs = C * (1 + CEps)) this is equivalent to 1 / Yhat* Yha
error(CEps = 1) --> additive
as I mentioned do not use the 1/Y*Y ( since raw observed data will propagate unwanted error)
2/ sequential dual absorption
I have written the sequential dual absorption as followed:
deriv(Aa = - K0 -K1 * Aa)
deriv(A1 = K0 + K1 * Aa - K10 * A1 - K12 * A1 + K21 * A2)
deriv(A2 = K12 * A1 - K21 * A2)
dosepoint(A1, bioavail = Fr, duration = Tau)
dosepoint(Aa, bioavail = 1-Fr, tlag = Tau)
Where A1is always the central compartment.
Looking to this model, I have been told that it should perhaps have been written:
deriv(Aa1=-K0)
deriv(Aa2=-K1*Aa2)
deriv(A1=K0+K1*Aa2-K10*A1-K12*A1+K21*A2)
deriv(A2=K12*A1-K21*A2)
dosepoint(Aa1,bioavail=Fr,duration=tau)
dosepoint(Aa2,bioavail=(1-Fr),tlag=tau)
C=A1/V
Which one is correct? Writing “duration”, from where to where is going the 0-order flow? What is the difference between these following dosepoint ?
##########################
you do not need to include zero order rates into your differential equations...
imagine that the first order dose goes to Aa then it will be absorbed via ka from Aa to A1
while the zero order part will go directly to A1
the tag and duration help you to modify the order of events
#########################
deriv(Aa=-Ka*Aa)
deriv(A1=Ka*Aa-K10*A1-K12*A1+K21*A2)
# the zero order part is implied using the dosepoint
deriv(A2=K12*A1-K21*A2)
dosepoint(A1,bioavail=Fr,duration=tau) # zero order to A1 with duration tau
dosepoint(Aa,bioavail=(1-Fr),tlag=tau)
# remaining part of dose going into Aa after a tau lag it will be absorbed with a Ka *Aa rate
C=A1/V
dosepoint(A1, bioavail = Fr, duration = Tau)
dosepoint(Aa, bioavail = 1-Fr, tlag = Tau)
##########################
# FR * Dose that was mapped to A1 goes into A1
# 1 -FR *Dose that was mapped to Aa goes to Aa this is a bolus into Aa then it will be absorbed with ka as per the differential equation linking Aa and A1
dosepoint(Aa1,bioavail=Fr,duration=tau)
dosepoint(Aa2,bioavail=(1-Fr),tlag=tau)
dosepoint(Aa,bioavail=Fr,duration=tau)
dosepoint2(Aa,bioavail=(1-Fr),tlag=tau)
where I always consider Aa as subcutaneous compartment and A1 as central compartment.
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3/ Use of graphical model building tool
I try to use the graphical tool as well.
For example, I add a Tlag to Aa compartment, I fill in the blank with a time parameter called Tau that I want to estimate. However, this new parameter does not appear neither in the parameter tab nor in the initial estimate tab. Did I do something wrong? Or should I then edit it as textual model and add this fixef ?
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in graphical model right click on you model window and select insert parameter
than name it the corresponding name.
# let me know if you need anything else.
you can call me at 514 475 9339 for a chat
I am located at the east coast time zone