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Double Peak PK modeling


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#1 jgjguo@gmail.com

jgjguo@gmail.com

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Posted 03 August 2020 - 05:01 PM

I am working on a PK model for a PK profile with double peaks .  I found a paper reporting the same kind of case with two gastric emptying rates.  I am not sure how to restrict the time ranges those are associated with different gastric emptying time (highlighted on attached paper. Could you do me a favor to take a look at my model and see how to improve it?  In my model, T1 is tend and T2 is tlag those are mentioned on attached paper respectively. It sounds like kg2 is not well defined on my model.

 

Thanks

 

Jian

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#2 Simon Davis

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Posted 04 August 2020 - 08:14 AM

Jian, here is some proposed code.

test(){
kg = t < T1? kg1:
t > T1+deltaT? kg1:
kg2

deriv(Ast = -kg * Ast)
deriv(Aint = kg * Ast - ka * Aint)
deriv(Cp = (ka *Aint + k21 * Aper)/ V - (k12 + ke) * Cp)
deriv(Aper = k12 * Cp * V - k21 * Aper)
dosepoint(Ast)
error(CEps = 0.1)
observe(CObs = Cp*(1 + CEps))
fixef(ka = c(, 4.5, ))
fixef(k12 = c(, 5.8, ))
fixef(k21 = c(, 0.9, ))
fixef(ke = c(, 1.7, ))
fixef(V = c(, 0.7, ))
fixef(kg1 = c(, 0.5,))
fixef(kg2 = c(, 0.1,))
# T1 is Tend
fixef(T1 = c(, 3, ))
# T2 is Tlag
# deltaT is Tlag - Tend
fixef(deltaT = c(0, 3, ))
}

I would also suggest that you could instead call T1, Tend in the code etc. then the code is more transparent


Also in your model it is possible to append all your doses into one worksheet and dit them together, you can even run them as Naive pool population without an NLME license if you feel the individual data is too sparse to fit well. that would be better than meaning the data first I think.

[color=#000000][font=calibri][size=2] Simon.

Edited by Simon Davis, 04 August 2020 - 08:22 AM.





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