Re: Problem to implement a change in transfer rate after event during measurement period

Dear Andreas MTIME is used for estimation of an model event time. Hence you use it if you do not know the time, but it appears you do know the time. If the time is the same for all individuals, and I would simply use the following code: IF(TIME.LE. xxx) THEN K12=THETA(..) ELSE K12=THETA(..) ENDIF If the time is different for different individuals, perhaps you can add a column with a flag of some sort in your dataset where this event occurs and replace TIME in the above code with your flag. Make sure you put the flag at the event time, and for all the subsequent records for that individual. So all your records before EVID=2 in your dataset can have FLAG=0, then from EVID =2 onwards you put FLAG=1 and code your control stream as follows: IF(FLAG.EQ.0) K12=THETA(..) IF(FLAG.EQ.1) K12=THETA(..) Hope this helps. Emmanuel >>> Steingötter Andreas 07/27/10 7:11 PM >>> Dear NONMEM users I would like to include a change in a rate constant after an event that occurred at a defined time during the measurements for each individual. As you can see from the data example listed below, the model used is a two compartment model with a bolus input. I now use ADVAN7, however I understand that ADVAN2 might do as well. To achieve my goal, I included a record at that given time point with EVID=2, MVD=1 and DV = NA. From some examples in the users network I understood that I can use the MTIME parameter to implement this discrete change in K12. I am not sure if I correctly understood the use of MTIME and MTDIFF and if I really need to introduce another theta for MTIME. I hope someone with more experience on this topic can give me a hint or suggestion on how to best implement such a problem. Many thanks for any help Andreas $PROB 2 Compartments Meal and PDR $DATA penta_BT-Meal-pgs_evid.txt IGNORE=C $INPUT ID,TIME,DV,CMT,AMT,RATE,MDV,OCC,EVID $SUBROUTINES ADVAN7 $Model COMP = Meal COMP = PDR $PK IF (EVID.EQ.2) INFTIME = TIME MU_INF = THETA(5) ET_INF = ETA(4) MTIME(1) = DEXP(MU_INF + ET_INF)+INFTIME MTDIFF = 1 MU_K12 = THETA(1)+(1-MPAST(1))+THETA(4)*MPAST(1) ; new meal rate constant theta(5) after switching off the penta infusion ET_K12 = ETA(1) MU_K20 = THETA(2) ET_K20 = ETA(2) MU_F2 = THETA(3) ET_F2 = ETA(3) K12 = DEXP(MU_K12 + ET_K12) ; meal to PDR K20 = DEXP(MU_K20 + ET_K20) ; elimination F2 = MU_F2 + EXP(ET_F2) ; bioavailability PDR S2 = F2 CL = K20*S2 $ERROR Y=F*(1+ERR(1))+ERR(2) IPRED = F IRES = DV-IPRED ; individual-specific residual IWRES = IRES ; individual-specific weighted residual $THETA (-10.,-4., 0.) ;logK12 (-10.,-2., 0.) ;logK20 (0.0, 0.4, 5.0) ;F2 (-10.,-4., 0.) ;logK12_2 (-5.,0.1, 5.) ;logmtime $OMEGA 0.3 ;logETA_K12 0.3 ;logETA_K20 0.2 ;ETA_F2 0.1 ;ETA_inftime $SIGMA 1. 20. ID TIME DV CMT AMT RATE MDV OCC EVID 1 0.000 . 1 500 0 1 0 1 1 0.000 5.00e+02 1 . . 0 0 0 1 0.736 0.00e+00 2 . . 0 0 0 1 2.177 5.04e-01 2 . . 0 0 0 1 7.008 4.87e+00 2 . . 0 0 0 1 12.052 1.05e+01 2 . . 0 0 0 1 14.000 4.09e+02 1 . . 0 0 0 1 16.768 1.09e+01 2 . . 0 0 0 1 20.000 3.25e+02 1 . . 0 0 0 1 23.942 9.63e+00 2 . . 0 0 0 1 24.000 3.19e+02 1 . . 0 0 0 1 28.780 9.24e+00 2 . . 0 0 0 1 29.000 3.08e+02 1 . . 0 0 0 1 33.540 8.48e+00 2 . . 0 0 0 1 34.000 2.92e+02 1 . . 0 0 0 1 39.000 2.97e+02 1 . . 0 0 0 1 43.293 8.41e+00 2 . . 0 0 0 1 44.000 2.79e+02 1 . . 0 0 0 1 45.671 7.81e+00 2 . . 0 0 0 1 48.219 8.15e+00 2 . . 0 0 0 1 50.000 2.70e+02 1 . . 0 0 0 1 50.659 8.14e+00 2 . . 0 0 0 1 54.000 2.57e+02 1 . . 0 0 0 1 56.000 . 1 . . 1 0 2 1 59.000 2.70e+02 1 . . 0 0 0 1 64.000 2.55e+02 1 . . 0 0 0 ---------------------------------------------------------------------------------------------------------------------------------------- Andreas Steingötter, PhD Institut for Biomedical Engineering Klinik für Gastroenterologie und Hepatologie Divisions of Bioimaging and MRI Technology Department Innere Medizin University and ETH Zurich Universitätsspital Gloriastrasse 35 Rämistrasse 100 CH - 8092 Zurich CH - 8091 Zürich Tel. +41 44 255 5684 Tel. +41 44 255 5684 Fax +41 44 632 1193 Fax +41 44 255 4591 Email [email protected] Email [email protected] ### UNIVERSITY OF CAPE TOWN This e-mail is subject to the UCT ICT policies and e-mail disclaimer published on our website at http://www.uct.ac.za/about/policies/emaildisclaimer/ or obtainable from +27 21 650 4500. This e-mail is intended only for the person(s) to whom it is addressed. If the e-mail has reached you in error, please notify the author. If you are not the intended recipient of the e-mail you may not use, disclose, copy, redirect or print the content. If this e-mail is not related to the business of UCT it is sent by the sender in the sender's individual capacity. ###