4 replies to this topic

[Manoj Chiney]

Hi,

I have IV and PO data from 3 animals. I was interested in fitting a simultaneous IV and PO model using Pheonix. In my source file I have added an ID for the type of dosing i.e. I sort the data using 1,2 ( all 3 animals that receive IV =1 and all three animals that receive PO = 2). Also, I have made a separate column for dose. My code is below.

 

test(){

deriv(Aa = - Ka * Aa - Km * Aa)

deriv(A1 = Ka * Aa - Ke * A1 - K12 * A1 + K21 * A2)

deriv(A2 = K12 * A1 - K21 * A2)

dosepoint(Aa, bioavail = (F))

dosepoint(A1)

C1 = A1 / V

error(CEps = 1)

observe(CObs1 = C1 * (1 + CEps))

stparm(Ka = tvKa * exp(nKa))

stparm(F = tvF)

stparm(V = tvV * exp(nV))

stparm(Ke = tvKe * exp(nKe))

stparm(K12 = tvK12 * exp(nK12))

stparm(K21 = tvK21 * exp(nK21))

fixef(tvKa= c(0, 0.021, ))

fixef(tvF = c(0, 0.3,1 ))

fixef(tvKm = c(0, 0.041, ))

fixef(tvV = c(, 135, ))

fixef(tvKe = c(0, 0.071, ))

fixef(tvK12 = c(0, 0.027,0.5 ))

fixef(tvK21 = c(0, 0.0028,0.5 ))

ranef(diag(nV, nKe, nKa, nK12, nK21) = c(1, 1, 1, 1, 1, 1, 1))

}

 

However, my model estimates a Ka and F for the IV group too.

 

Can anyone send me a test file for simultaneous IV and PO dosing and also let me know what I am missing in my code.

 

Thank you.

[serge guzy]

Dear Chine002

The estimates of Ka for the IV group are not relevant.

For IV you have V to be used as estimate while V/F will be the apparent volume of distribution for the PO subjects.

If the estimates are done using the tab "structural parameters", I believe that the estimates of F and Ka for the IV group should be similar to the population mean as there is no information about these parameters for the IV group.

Note that km in your code is not relevant as you do not have PO observations but only Plasma observations.

 

Best Regards

Serge

 

test(){

#deriv(Aa = - Ka * Aa - Km * Aa)

# should be

deriv(Aa = - Ka * Aa )

 

deriv(A1 = Ka * Aa - Ke * A1 - K12 * A1 + K21 * A2)

deriv(A2 = K12 * A1 - K21 * A2)

dosepoint(Aa, bioavail = (F))

dosepoint(A1)

C1 = A1 / V

error(CEps = 1)

observe(CObs1 = C1 * (1 + CEps))

stparm(Ka = tvKa * exp(nKa))

stparm(F = tvF)

stparm(V = tvV * exp(nV))

stparm(Ke = tvKe * exp(nKe))

stparm(K12 = tvK12 * exp(nK12))

stparm(K21 = tvK21 * exp(nK21))

fixef(tvKa= c(0, 0.021, ))

fixef(tvF = c(0, 0.3,1 ))

#fixef(tvKm = c(0, 0.041, ))

fixef(tvV = c(, 135, ))

fixef(tvKe = c(0, 0.071, ))

fixef(tvK12 = c(0, 0.027,0.5 ))

fixef(tvK21 = c(0, 0.0028,0.5 ))

ranef(diag(nV, nKe, nKa, nK12, nK21) = c(1, 1, 1, 1, 1, 1, 1)) }

 

However, my model estimates a Ka and F for the IV group too.

 

Can anyone send me a test file for simultaneous IV and PO dosing and also let me know what I am missing in my code.

 

Thank you.

[Manoj Chiney]

Thank you Serge. I am still working on it. I will let you know how things turn out.

[Patrick Sterkens]

Is there any follow-up on this topic. I would be very interested to see a working model, as I have exactly the same question: modeling iv & po simultaneously in the same animal.

[serge guzy]

HERE WE GO WITH A WORKING MODEL. PLEASE LOOK AT INPUT POTIONS AS USED ADDL AND II. Let me know if all is clear. If n, will add a full explanation of all steps. best Serge [file name=IV_ORAL_COMBINED_WITH_ADDL.phxproj size=1117516]http://pharsight.com/extranet/media/kunena/attachments/legacy/files/IV_ORAL_COMBINED_WITH_ADDL.phxproj[/file]

Attached Files

•  IV_ORAL_COMBINED_WITH_ADDL.phxproj   1.07MB   258 downloads

Edited by Simon Davis, 09 December 2019 - 02:19 PM.
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