# Fitting Brain and Plasma concentrations

**URL:** <https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014>\
**Category:** Modelling and Simulation\
**Created:** [September 2, 2016, 8:37am UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014 "2016-09-02T08:37:42Z")\
**Posts on this page:** 8\
**Page:** 1

<div class="post-metadata">

**Author:** ![harishkk](https://avatars.discourse-cdn.com/v4/letter/h/54ee81/32.png) [@harishkk](https://forum.certara.com/u/harishkk)\
**Post date:** [September 2, 2016, 8:37am UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/1 "2016-09-02T08:37:42Z")

</div>

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](https://forum.certara.com/uploads/short-url/zYxHYcIwLVLAuRrHX4ZpiuFgqWi.pdf) (596 KB)[intranasal L\_C.phxproj](https://forum.certara.com/uploads/short-url/qNTd3ic0VncptFWRZV3nkOCxOMO.phxproj) (141 KB)

---

<div class="post-metadata">

**Author:** ![SimonDavis](https://avatars.discourse-cdn.com/v4/letter/s/d9b06d/32.png) [@SimonDavis](https://forum.certara.com/u/SimonDavis)\
**Post date:** [September 2, 2016, 9:10am UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/2 "2016-09-02T09:10:26Z")

</div>

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](https://forum.certara.com/uploads/short-url/gBMxFTpFjSyRU55LEIN5Mq2hkbx.phxproj) (409 KB)

---

<div class="post-metadata">

**Author:** ![harishkk](https://avatars.discourse-cdn.com/v4/letter/h/54ee81/32.png) [@harishkk](https://forum.certara.com/u/harishkk)\
**Post date:** [September 2, 2016, 9:28am UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/3 "2016-09-02T09:28:57Z")

</div>

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

---

<div class="post-metadata">

**Author:** ![minhaj](https://avatars.discourse-cdn.com/v4/letter/m/a698b9/32.png) [@minhaj](https://forum.certara.com/u/minhaj)\
**Post date:** [September 2, 2016, 9:35am UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/4 "2016-09-02T09:35:53Z")

</div>

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](https://forum.certara.com/uploads/short-url/fxFnRWQEwouKqhe4uadwTFjVaba.phxproj) (1.25 MB)

---

<div class="post-metadata">

**Author:** ![SimonDavis](https://avatars.discourse-cdn.com/v4/letter/s/d9b06d/32.png) [@SimonDavis](https://forum.certara.com/u/SimonDavis)\
**Post date:** [September 2, 2016, 10:19am UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/5 "2016-09-02T10:19:28Z")

</div>

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](https://forum.certara.com/uploads/short-url/qVOHszMbOF0rjPw4b4fBHxBKNdV.phxproj) (727 KB)

---

<div class="post-metadata">

**Author:** ![kmbbertm](https://avatars.discourse-cdn.com/v4/letter/k/3ab097/32.png) [@kmbbertm](https://forum.certara.com/u/kmbbertm)\
**Post date:** [October 25, 2016, 4:27pm UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/6 "2016-10-25T16:27:11Z")

</div>

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

([**intranasal L\_C\_serge\_corrected.phxproj**](https://support.certara.com/forums/index.php?app=core&module=attach&section=attach&attach_id=2719) ), 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

---

<div class="post-metadata">

**Author:** ![minhaj](https://avatars.discourse-cdn.com/v4/letter/m/a698b9/32.png) [@minhaj](https://forum.certara.com/u/minhaj)\
**Post date:** [October 25, 2016, 5:36pm UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/7 "2016-10-25T17:36:21Z")

</div>

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, ))  
}

---

<div class="post-metadata">

**Author:** ![minhaj](https://avatars.discourse-cdn.com/v4/letter/m/a698b9/32.png) [@minhaj](https://forum.certara.com/u/minhaj)\
**Post date:** [October 25, 2016, 5:36pm UTC](https://forum.certara.com/t/fitting-brain-and-plasma-concentrations/3014/8 "2016-10-25T17:36:53Z")

</div>

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

Do you need the data set too?  
â€‹Best REgards

Serge
