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The following message was posted to: PharmPK
Dear Group Members,
I am trying to model one PK/PD data in phoenix. PD data is showing a
time lag of two hour. I want to capture the time lag by using "IF and
ELSE" kind of statement, which is k/a "Sequence/sleep" statement in
Phoenix.
Here is the code:
}
test(){
deriv(A1=-ka*A1)
deriv(A1=ka*A1-kel*A2)
deriv(A3=kng-((Emax*A2)/(EC50+A2))* A3)
C=A2/V
dose point (A2)
error(CEps=1)
observe(CObs = C+CEps)
stparm(V = (tvV))
stparm(kel = (tvkel))
stparm(ka= (tvka))
fixef(tvV = c(, 3.8, ))
fixef(tvkel = c(, 1.24, ))
fixef(tvka = c(, 0.5, ))
}
I would appreciate guidance and appropriate suggestions to this problem.
Regards
Raj.
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The following message was posted to: PharmPK
Dear Raj,
You can do this in several ways: sequence/sleep; conditional assignment; or booleans. The
sequence/sleep method is nice because it makes the integrator run faster.
First we need to fix a couple things in the model, though:
- you have two equations for A1, the second one should say deriv(A2 = ka*A1-kel*A2)
- dosepoint is one word, and I presume you intend to dose into the absorption compartment
"A1".
- usually the emax model for PD will be a function of concentration. Do you want to
change "A2" to "C"?
- kng is undefined in your model. Is it a constant, or fixed effect?
Now, to set up the timelag on A3:
- modify the A3 derivative to have a flag variable "flag" (name not important):
deriv(A3=kng-flag*((Emax*A2)/(EC50+A2))* A3)
- add a declaration for "flag": "double(flag)"
- add a sequence statement:
sequence{flag=0;sleep(2);flag=1;}
This model will cause the Emax model to "turn on" after 2 hours. When it does so, it will
use the current value of A2 as opposed to a delayed A2 value. Note that you can replace
the "2" with a variable name to estimate the delay as needed.
There are other options for modeling a delay that you might consider:
- biophase model
- turnover model
Cheers,
Jason Chittenden
Director, Product Development
Certara(tm)
Implementing Translational Science
5625 Dillard Drive, Suite 205, Cary NC 27518
Certara: The name behind the names you know
Tripos - Simcyp - Pharsight
www.certara.com
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