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)
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.
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.
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.
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,
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?