How to put dose point in PBPK simulation

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Posted 11 June 2013 - 03:34 AM

Hi,

I am doing a PBPK simulation to see portal and plasma conc. I am facing problem in poting Dose point/GI equation. Equation are written below;

Kindly let me know about GI equation and initial condition for GI

Init GI=0

Init Portal=0

Init Liver=0

Init Plasma=0

d/dt(GI)= -Dnmole*ka*FaFg

d/dt(Portal) = (Qp*Plasma+Dnmole*ka*FaFg*exp(-ka*time)-Qp*Portal)/Vp

d/dt(Liver) = ( Qa*Plasma + Qp*Portal-Qh*(Liver/Kp)-CLh*(Liver/Kp))/Vl

d/dt(Plasma) = (Qh*(Liver/Kp)-Qh*Plasma-CLnh*Plasma)/Vc

Qh=(55*60)/1000

Qp=(32.9*60)/1000

Qa=Qh-Qp

CLnh=(5*60)/1000

CLh=(45*60)/1000

Vc=31/1000

Vl=78/1000

Vp=8/1000

ka=1.5

FaFg=0.9

Kp=1

Dose=5

Dnmole=Dose*1000000/MWt

MWt=500 [file name=gi_portal_liver_plasma.xls size=11264]http://pharsight.com/extranet/media/kunena/attachments/legacy/files/gi_portal_liver_plasma.xls[/file]

#2 serge guzy

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Posted 11 June 2013 - 05:31 AM

Dear Raj

Can you please share your phoenix current code and I can then debug. The equations you wrote are not phoenix based. I am not sure I understand your initial conditions. Is the dosepoint in the GI compartment? Your code even without data will help me identifying the potential problems.

Best Regards;

Serfge

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Posted 11 June 2013 - 06:47 AM

Hi Dr Serge,

This is phoenix converted code.

test(){

deriv(GI = -Dnmole*ka*FaFg)

deriv(Portal = Qp*Plasma+Dnmole*ka*FaFg*exp(-ka*t)-Qp*Portal/Vp)

deriv(Liver = Qa*Plasma + Qp*Portal-Qh*(Liver/Kp)-CLh*(Liver/Kp)/Vl)

deriv(Plasma = Qh*(Liver/Kp)-Qh*Plasma-CLnh*Plasma/Vc)

dosepoint(GI)

C1=Dnmole

error(C1Eps = 1)

observe(C1Obs = C1 + C1Eps)

C2=Portal

error(C2Eps = 1)

observe(C2Obs = C2 + C2Eps)

C3=Liver

error(C3Eps = 1)

observe(C3Obs = C3 + C3Eps)

C4=Plasma

error(C4Eps = 1)

observe(C4Obs = C4 + C4Eps)

Dnmole=10000

Qh=3.3

Qp=1.974

Qa=Qh-Qp

CLnh=0

Vp=0.008

Vl=0.078

Vc=0.031

FaFg=0.9

stparm(ka = (tvka))

stparm(Kp = (tvKp))

stparm(CLh = (tvCLh))

fixef(tvka = c(, 1.5, ))

fixef(tvKp = c(, 1, ))

fixef(tvCLh = c(, 2.7, ))

}

Dose input in GI and ut absobed as Dose*ka*FaFg*exp(-ka*t) in portal and goes in liver and systemic ie plasma again coming from plasma to potal

My question about is how to put dose point in GI compartment........ and get the accurate plasma and portal profile

Thanks Raj

#4 serge guzy

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Posted 11 June 2013 - 09:52 AM

Dear Raj

You had Dnmole used before being defined. I changed the code and added a random effect to enable simulation using the population interface.

It is attached.

I hope it helps.

best

Serge [file name=raj_phsio_OFFICIAL.phxproj size=694863]http://pharsight.com/extranet/media/kunena/attachments/legacy/files/raj_phsio_OFFICIAL.phxproj[/file]

Attached Files

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Posted 11 June 2013 - 10:11 AM

Hi Dr Serge,

I am unable to open the file, Could you pls send me the code in text form.

Thanks

Raj

#6 serge guzy

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Posted 11 June 2013 - 10:14 AM

Here we go

test(){
deriv(GI = -Dnmole*ka*FaFg)
deriv(Portal = Qp*Plasma+Dnmole*ka*FaFg*exp(-ka*t)-Qp*Portal/Vp)
deriv(Liver = Qa*Plasma + Qp*Portal-Qh*(Liver/Kp)-CLh*(Liver/Kp)/Vl)
deriv(Plasma = Qh*(Liver/Kp)-Qh*Plasma-CLnh*Plasma/Vc)

dosepoint(GI)
Dnmole=10000
C1=Dnmole
error(C1Eps = 1)
observe(C1Obs = C1 + C1Eps)
C2=Portal
error(C2Eps = 1)
observe(C2Obs = C2 + C2Eps)
C3=Liver
error(C3Eps = 1)
observe(C3Obs = C3 + C3Eps)
C4=Plasma
error(C4Eps = 1)
observe(C4Obs = C4 + C4Eps)

Qh=3.3
Qp=1.974
Qa=Qh-Qp
CLnh=0
Vp=0.008
Vl=0.078
Vc=0.031
FaFg=0.9
stparm(ka = (tvka*exp(nka)))
stparm(Kp = (tvKp))
stparm(CLh = (tvCLh))

fixef(tvka = c(, 1.5, ))
fixef(tvKp = c(, 1, ))
fixef(tvCLh = c(, 2.7, ))
ranef(diag(nka)=c(0.0001))
}

One other comment Raj, we are constantly improving the visual debugger as you can see in this screenshot from the 6.4 pre-release. Simon

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