Fitting Brain and Plasma concentrations

Phoenix Certara Forums Modelling and Simulation
1

Hello All,

Iam trying to fit brain and plasma concentrations simultaneously following intranasal administration using the graphical model mentioned in the attached paper, Iam also attaching the project file for review,

Can any body help me to fit the data to the model as proposed in the paper

Thanks in advance

Regards

Harish

PK modelling of LD Nasal delivery.pdf (596 KB)intranasal L_C.phxproj (141 KB)

2

I haven’t looked at the paper but I did quickly restructure your data with a pivot so you had a separate column to map for plasma and brain; the model now runs

intranasal L_C.phxproj (409 KB)

3

Dear Simon,

Thanks for your quick edits, is there any way where by we could run simultaneously 2 matrices data ie brain and plasma together for all the groups together, bcoz as i see when i tried to run the model based on the pivoted sheet, i could only see 1 group’s fit (brain and plasma)

if you can guide me further it would help

Regards

Harish

4

Dear Harish

Please see the attached project I made that can serve as a template for future modeling.

1:You put a dose in the brain compartment which I believe is not appropriate.

2: I assume 4 different patients because I am not sure if it was cross over one patient, 2 patients, etc..

It does not change how to built the structural model.

If it is one patient only, then we need to reset the compartments to their initial values every time we have a new dose which is what I did with the reset function and by uncheck the sort button

3: For both “one individual” and “4 individuals” I built the model using the graphical option (see attached) and I assume a treatment effect on both Cl and Volume

4: I fit both models and the results are not too bad. Of course the model we used limit the ability to get perfect fit but the idea is there.

Look at it and come back to me if you need further clarifications about what I did.

best Regards

Serge

intranasal L_C_serge_corrected.phxproj (1.25 MB)

5

What you mean in population mode like the attached?

Do you have an NLME license, if not you will only be able to view the results but not re-run them. I haven’t revised anything to optimise the model

Simon

intranasal L_C_pop.phxproj (727 KB)

6

I am receiving an error message in trying to open the corrected phxproj file

(intranasal L_C_serge_corrected.phxproj ), citing that the file was created in a new version of the software. Is there a work around for this?, I am looking to apply a similar sort of model to fit plasma & csf concentrations.

Many thanks

Kirk Bertelsen

7

test(){
deriv(A1 = - (Cl * C) + (Aa * Ka)- (A1 * K12- A2 * K21))
urinecpt(A0 = (Cl * C))
deriv(Aa = - (Aa * Ka))
deriv(A2 = (A1 * K12- A2 * K21))
C = A1 / V
dosepoint(Aa, idosevar = AaDose, infdosevar = AaInfDose, infratevar = AaInfRate)
error(CEps = 1)
observe(Cplasma = C + CEps)
V2 = V * K12 / K21
C2 = A2 / V2
error(CEpsbrain = 1)
observe(Cbrain = C2 + CEpsbrain)

stparm(V = tvV)
stparm(Cl = tvCl)
stparm(Ka = tvKa)
stparm(K12 = tvK12)
stparm(K21 = tvK21)
fixef(tvV = c(, 1, ))
fixef(tvCl = c(, 1, ))
fixef(tvKa = c(, 1, ))
fixef(tvK12 = c(, 1, ))
fixef(tvK21 = c(, 1, ))
}

8

There were some errors in the model and I fixed it.

Do you need the data set too?
​Best REgards

Serge