Dear All,
I have oral pharmacokinetic data(@different doses) of Compound X following oral administration in rat and its showing Enterohepatic Recirculation(second peak).
Can any one suggest me how to perform Pk modeling in Pheonix model 6.4 or WNL Classical?? for compound showing Enterohepatic Recirculation(second peak)
Best Regards,
Vallabh Mahajan
Please look at page 45 of the Phoenix 1.4 Modeling Language Reference Guide (Help>Documents>…);
Modeling discontinuous events
There are many kinds of models involving discrete time-based events at which discontinuous changes can occur in a model. The following is a partial example of an entero-hepatic reflux model.
1 deriv(a = -ak10 - ak1b + g*kg1)
# central cpt
2 deriv(b = a*k1b - qbg)
# bile cpt
3 deriv(g = qbg - g*kg1)
# gut cpt
4 double(qbg)
#qbg is flow rate from bile to gut
5 stparm(tCycle=…, tReflux=…)
# times are parameters
# introduce the time sequence:
6 double(i)
7 sequence{
8 i = 0;
9 while(i<10){
10 i = i + 1;
11 qbg = 0;
12 sleep(tCycle - tReflux);
13 qbg = (b/tReflux);
14 sleep(tReflux);
15 qbg = 0;
16 }
17 }
The model has three compartments: a for plasma, b for bile, and g for gut. Normally the compound flows from gut to plasma and from plasma to bile, as well as flowing through the normal elimination path. There is also a flow from bile to gut, which is the reflux path. This is modeled as a zero-order flow of rate qbg. The flow is turned on and off to model the reflux.
Lines 1-3 give the differential equations for the three compartments. The variable qbg is a variable representing the flow rate from bile to gut, and it is initially zero.
Line 4 declares a variable, qbg, which will be used in some of the equations and statements.
Line 5 designates that there are two structural parameters giving the cycle time between reflux events (tCycle) and the duration (tReflux) of each event.
Line 6 declares a variable, i, which will be used in some of the equations and statements.
Lines 7-17 are grouped with the sequence keyword. This introduces timesequenced procedure into the model.
Line 8 sets the initial value for the variable i to 0.
Line 9 groups the next 6 statements into a loop that will repeat up to 10 times.
Line 10 adds one to the value of i (number of iterations).
Line 11 sets the initial value for the variable qbg to 0.
Line 12 allows tCycle - tReflux time units to pass.
Line 13 turns on the reflux by setting qbg to the rate necessary to empty the bile compartment within duration tReflux.
Lines 14-15 say to wait for tReflux time units, and then turn off the flow, after which the cycle repeats.
Dear Vallabh
Please fond attached a project example with explanations that should help you. Let me know if you need further clarifications.
best Regards
Serge
soraf_pk.phxproj (402 KB)Population pharmacokinetic_of_sorafnebit.pptx (570 KB)
Dear Simon and Serge
Thanks for kind reply
Can i edit as Graphical ?? because textual showed error in phoenix model
Please help me to draw a graphical model for Enterohepatic Recirculation
best Regards,
Vallabh Mahajan
Dear Vallabh
You cannot do that graphically as the sequence statement is used for that purpose.
best Regards
Serge
Please let us know the error message you saw in text mode, since it may be a simple typo or other syntax error.
perhaps just attach your model project
Simon.
Can you copy to the forum the pml you are using. We may find the error just from the code.
Best
serge
Dear Simon and Serge,
Please find attached data for modeling in phoenix
I tried in Graphical mode
please check and let me correct
Best Regards,
Vallabh Mahajan
Dear Simon and Serge,
Please find attached data for modeling in phoenix
I tried in Graphical mode
please check and let me correct
Best Regards,
Vallabh Mahajan
CPD X.phxproj (1.14 MB)
Hi Serge
I tried modeling the EHC of my drug dosed orally at 40mg to humans under fed state
Iam attaching the project file for your review
Let me know how do we do the EHC modelling,
I tried doing it in ASCII but of no luck
Regards
Harish
soraf_pk.phxproj (437 KB)
Dear Vallabh
You should not use an elimination compartment to pass drug from plasma that compartment when allowing it to return to plasma. I fixed your model, add multiplicative error and sued clearance parametrization. That is the standard way.
Look at the last model.
best Regards
Serge
CPD X.phxproj (2.61 MB)
Dear Serge
Thanks for kind reply.
Best Regards,
vallabh Mahajan
Hi Sergy & Vallabh,
@Vallabh
The model didn’t serve your purpose of EHC i guess!! If yes then share the graphical/textual model let me try
@Serge
I have earlier shared the WNLproject file on EHC modelling, can you please share your comments on it
Regards
Harish
Hi Harish
Where is your project? Can you share it and put it on the forum for me to review?
Thanks
Serge
Hello Serge,
PFA my phoenix project file, Iam trying to do EHC modelling
Regards
Harish
soraf_pk.phxproj (437 KB)
Dear Harish
What is the problem here? Is it the computing time that is too long?
I am juts trying to see if it is a time issue or something else. It seems to be similar to the code I generated a while ago.
best Regards
Serge
Strange. I cannot reproduce that project that worked a while ago. I will check again and send it to the developers if still an issue. We have soon an upcoming version I will test too.
best Regards
Serge
Ok I got it. In 14 patch a bug has been created and fixed in the upcoming version (70).
The go around is just to write instead of
while(1)
while(t<240)
240 is the final time.
Try it and let me know.
best
Serge
Hi Serge,
Thanks for looking into the project file, within the file you have ABS 40mg data which iam looking to model using EHC code shared by you and editing the code with the line told by you but still there is no luck,
Can you help me in that
Regards
Harish
Dear Harish
I am not sure I understood what you ask. Can you clarify and tell me how I can assist you more. The project I sent you where you change while(1) to while(t<240) should work if you have the 14 version with the patch. Do you have the patch installed?
Best Regards
Serge