Simulate simultaneous zero and first order absorption

On Wed, Mar 5, 2014 at 9:51 PM, Justus Bingham < [email protected]> wrote: > Dear NMUSERS, > > I am having problems simulating simultaneous zero and first order > absorption. Here is my model and data file. Every time it only reads in the > second dose record and simulates based on that record. I have tried this on > three different computers running NONMEM. CLI, VI and KAI are individual > nonmem PK parameter estimates for subjects from sparse data using an > established population model setting MAXEVAL=0. I am trying to simulate a > full profile for each subject based on their PK parameters. > > $PROB SIMULATE > $INPUT C ID CMT AMT EVID TIME RATE II SS CLI VI KAI DV > > $DATA sim.csv IGNORE=C > > $SUBROUTINES ADVAN4 TRANS4 > > > $PK > > CL = CLI > V2 = VI > Q = 0.02 > V3 = 0.9 > KA = KAI > D2 = 6 > > F1=0.7 > F2=0.3 > ALAG1=0.125 > ALAG2=0.125 > > > > $ERROR CALLFL=0 > > IPRED=0 > IF(CMT.EQ.2) IPRED=LOG((A(2)+0.000001)/V2)+ERR(1) > Y = IPRED > IRES = DV - IPRED > IWRES=IRES ;W=1 for additive error model > > $OMEGA > > 0 FIXED > > $SIGMA > 0 FIXED > > $SIMULATION ONLY (12345) > > $TABLE ID TIME EVID IPRED > NOPRINT FILE=NCA > > CIDCMTAMTEVIDTIMERATEIISSCLIVIKAIDV.1110001002410.050.30.05..12100010-2241 > 0.050.30.05..12.00.01...0.050.30.05..12.00.5...0.050.30.05..12.01...0.05 > 0.30.05..12.01.5...0.050.30.05..12.02...0.050.30.05..12.02.5...0.050.30.05 > ..12.03...0.050.30.05..12.04...0.050.30.05..12.05...0.050.30.05..12.06... > 0.050.30.05..12.07...0.050.30.05..12.08...0.050.30.05..12.09...0.050.30.05 > ..12.010...0.050.30.05..12.011...0.050.30.05..12.012...0.050.30.05..12.014 > ...0.050.30.05..12.016...0.050.30.05..12.018...0.050.30.05..12.020...0.05 > 0.30.05..12.022...0.050.30.05..12.024...0.050.30.05. > > Any help would be appreciated. > > Regards, > > Justus > -- Navin Goyal

________________________________________ From: [email protected] [[email protected]] On Behalf Of Navin Goyal [[email protected]] Sent: 06 March 2014 04:33 To: Justus Bingham Cc: nmusers Subject: Re: [NMusers] Simulate simultaneous zero and first order absorption Hi Justus, It may be that having SS as 1 on both records (for CMT 1 and CMT 2) leads to the first dose (or prior record) being cancelled out. If you keep the first record (CMT =1) at SS=1 and the next record (CMT=2) as SS=0 (and hence II=0 as well) it should reset the system at the beginning of CMT 1 dose and then follow up with CMT 2 dose without resetting the system again at second record. Kind regards Navin On Wed, Mar 5, 2014 at 9:51 PM, Justus Bingham <[email protected]<mailto:[email protected]>> wrote: Dear NMUSERS, I am having problems simulating simultaneous zero and first order absorption. Here is my model and data file. Every time it only reads in the second dose record and simulates based on that record. I have tried this on three different computers running NONMEM. CLI, VI and KAI are individual nonmem PK parameter estimates for subjects from sparse data using an established population model setting MAXEVAL=0. I am trying to simulate a full profile for each subject based on their PK parameters. $PROB SIMULATE $INPUT C ID CMT AMT EVID TIME RATE II SS CLI VI KAI DV $DATA sim.csv IGNORE=C $SUBROUTINES ADVAN4 TRANS4 $PK CL = CLI V2 = VI Q = 0.02 V3 = 0.9 KA = KAI D2 = 6 F1=0.7 F2=0.3 ALAG1=0.125 ALAG2=0.125 $ERROR CALLFL=0 IPRED=0 IF(CMT.EQ.2) IPRED=LOG((A(2)+0.000001)/V2)+ERR(1) Y = IPRED IRES = DV - IPRED IWRES=IRES ;W=1 for additive error model $OMEGA 0 FIXED $SIGMA 0 FIXED $SIMULATION ONLY (12345) $TABLE ID TIME EVID IPRED NOPRINT FILE=NCA C ID CMT AMT EVID TIME RATE II SS CLI VI KAI DV . 1 1 1000 1 0 0 24 1 0.05 0.3 0.05 . . 1 2 1000 1 0 -2 24 1 0.05 0.3 0.05 . . 1 2 . 0 0.01 . . . 0.05 0.3 0.05 . . 1 2 . 0 0.5 . . . 0.05 0.3 0.05 . . 1 2 . 0 1 . . . 0.05 0.3 0.05 . . 1 2 . 0 1.5 . . . 0.05 0.3 0.05 . . 1 2 . 0 2 . . . 0.05 0.3 0.05 . . 1 2 . 0 2.5 . . . 0.05 0.3 0.05 . . 1 2 . 0 3 . . . 0.05 0.3 0.05 . . 1 2 . 0 4 . . . 0.05 0.3 0.05 . . 1 2 . 0 5 . . . 0.05 0.3 0.05 . . 1 2 . 0 6 . . . 0.05 0.3 0.05 . . 1 2 . 0 7 . . . 0.05 0.3 0.05 . . 1 2 . 0 8 . . . 0.05 0.3 0.05 . . 1 2 . 0 9 . . . 0.05 0.3 0.05 . . 1 2 . 0 10 . . . 0.05 0.3 0.05 . . 1 2 . 0 11 . . . 0.05 0.3 0.05 . . 1 2 . 0 12 . . . 0.05 0.3 0.05 . . 1 2 . 0 14 . . . 0.05 0.3 0.05 . . 1 2 . 0 16 . . . 0.05 0.3 0.05 . . 1 2 . 0 18 . . . 0.05 0.3 0.05 . . 1 2 . 0 20 . . . 0.05 0.3 0.05 . . 1 2 . 0 22 . . . 0.05 0.3 0.05 . . 1 2 . 0 24 . . . 0.05 0.3 0.05 . Any help would be appreciated. Regards, Justus -- Navin Goyal ******************************************************************************************************************** This message may contain confidential information. If you are not the intended recipient please inform the sender that you have received the message in error before deleting it. Please do not disclose, copy or distribute information in this e-mail or take any action in reliance on its contents: to do so is strictly prohibited and may be unlawful. Thank you for your co-operation. NHSmail is the secure email and directory service available for all NHS staff in England and Scotland NHSmail is approved for exchanging patient data and other sensitive information with NHSmail and GSi recipients NHSmail provides an email address for your career in the NHS and can be accessed anywhere ********************************************************************************************************************

-----Original Message----- From: [email protected] [mailto:[email protected]] On Behalf Of Standing Joseph (GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUST) Sent: den 6 mars 2014 10:31 To: Navin Goyal; Justus Bingham Cc: nmusers Subject: RE: [NMusers] Simulate simultaneous zero and first order absorption Dear Justus, I agree with Navin that the first dose is ignored because the system is reset by the second dose SS/II. Navin's solution however I think will only set the CMT1 dosing as being at steady state and the CMT2 dose will be the first. When we encountered a similar problem the inelegant solution was not to use the II and SS data items, but to precede each dose with enough dummy doses to ensure the system would be at steady-state. i.e. if you think you might need 3 days to get to ss then: C ID CMT AMT EVID TIME RATE II SS CLI VI KAI DV . 1 1 1000 1 0 0 0 0 0.05 0.3 0.05 . . 1 2 1000 1 0 -2 0 0 0.05 0.3 0.05 . . 1 1 1000 1 24 0 0 0 0.05 0.3 0.05 . . 1 2 1000 1 24 -2 0 0 0.05 0.3 0.05 . . 1 1 1000 1 48 0 0 0 0.05 0.3 0.05 . . 1 2 1000 1 48 -2 0 0 0.05 0.3 0.05 . . 1 1 1000 1 72 0 0 0 0.05 0.3 0.05 . . 1 2 1000 1 72 -2 0 0 0.05 0.3 0.05 . . 1 2 . 0 72.01 . . . 0.05 0.3 0.05 . . 1 2 . 0 72.5 . . . 0.05 0.3 0.05 . This should work, but hopefully someone has a nicer solution. BW, Joe ________________________________________ From: [email protected] [[email protected]] On Behalf Of Navin Goyal [[email protected]] Sent: 06 March 2014 04:33 To: Justus Bingham Cc: nmusers Subject: Re: [NMusers] Simulate simultaneous zero and first order absorption Hi Justus, It may be that having SS as 1 on both records (for CMT 1 and CMT 2) leads to the first dose (or prior record) being cancelled out. If you keep the first record (CMT =1) at SS=1 and the next record (CMT=2) as SS=0 (and hence II=0 as well) it should reset the system at the beginning of CMT 1 dose and then follow up with CMT 2 dose without resetting the system again at second record. Kind regards Navin On Wed, Mar 5, 2014 at 9:51 PM, Justus Bingham <[email protected]<mailto:[email protected]>> wrote: Dear NMUSERS, I am having problems simulating simultaneous zero and first order absorption. Here is my model and data file. Every time it only reads in the second dose record and simulates based on that record. I have tried this on three different computers running NONMEM. CLI, VI and KAI are individual nonmem PK parameter estimates for subjects from sparse data using an established population model setting MAXEVAL=0. I am trying to simulate a full profile for each subject based on their PK parameters. $PROB SIMULATE $INPUT C ID CMT AMT EVID TIME RATE II SS CLI VI KAI DV $DATA sim.csv IGNORE=C $SUBROUTINES ADVAN4 TRANS4 $PK CL = CLI V2 = VI Q = 0.02 V3 = 0.9 KA = KAI D2 = 6 F1=0.7 F2=0.3 ALAG1=0.125 ALAG2=0.125 $ERROR CALLFL=0 IPRED=0 IF(CMT.EQ.2) IPRED=LOG((A(2)+0.000001)/V2)+ERR(1) Y = IPRED IRES = DV - IPRED IWRES=IRES ;W=1 for additive error model $OMEGA 0 FIXED $SIGMA 0 FIXED $SIMULATION ONLY (12345) $TABLE ID TIME EVID IPRED NOPRINT FILE=NCA C ID CMT AMT EVID TIME RATE II SS CLI VI KAI DV . 1 1 1000 1 0 0 24 1 0.05 0.3 0.05 . . 1 2 1000 1 0 -2 24 1 0.05 0.3 0.05 . . 1 2 . 0 0.01 . . . 0.05 0.3 0.05 . . 1 2 . 0 0.5 . . . 0.05 0.3 0.05 . . 1 2 . 0 1 . . . 0.05 0.3 0.05 . . 1 2 . 0 1.5 . . . 0.05 0.3 0.05 . . 1 2 . 0 2 . . . 0.05 0.3 0.05 . . 1 2 . 0 2.5 . . . 0.05 0.3 0.05 . . 1 2 . 0 3 . . . 0.05 0.3 0.05 . . 1 2 . 0 4 . . . 0.05 0.3 0.05 . . 1 2 . 0 5 . . . 0.05 0.3 0.05 . . 1 2 . 0 6 . . . 0.05 0.3 0.05 . . 1 2 . 0 7 . . . 0.05 0.3 0.05 . . 1 2 . 0 8 . . . 0.05 0.3 0.05 . . 1 2 . 0 9 . . . 0.05 0.3 0.05 . . 1 2 . 0 10 . . . 0.05 0.3 0.05 . . 1 2 . 0 11 . . . 0.05 0.3 0.05 . . 1 2 . 0 12 . . . 0.05 0.3 0.05 . . 1 2 . 0 14 . . . 0.05 0.3 0.05 . . 1 2 . 0 16 . . . 0.05 0.3 0.05 . . 1 2 . 0 18 . . . 0.05 0.3 0.05 . . 1 2 . 0 20 . . . 0.05 0.3 0.05 . . 1 2 . 0 22 . . . 0.05 0.3 0.05 . . 1 2 . 0 24 . . . 0.05 0.3 0.05 . Any help would be appreciated. Regards, Justus -- Navin Goyal ******************************************************************************************************************** This message may contain confidential information. If you are not the intended recipient please inform the sender that you have received the message in error before deleting it. Please do not disclose, copy or distribute information in this e-mail or take any action in reliance on its contents: to do so is strictly prohibited and may be unlawful. Thank you for your co-operation. NHSmail is the secure email and directory service available for all NHS staff in England and Scotland NHSmail is approved for exchanging patient data and other sensitive information with NHSmail and GSi recipients NHSmail provides an email address for your career in the NHS and can be accessed anywhere ********************************************************************************************************************

On the second dosing record, code SS = 2 for superposition of a second SS dose. SS = 1 will ignore prior dosing records. Best regards, Marc On Wed, Mar 5, 2014 at 9:51 PM, Justus Bingham < [email protected]> wrote: > Dear NMUSERS, > > I am having problems simulating simultaneous zero and first order > absorption. Here is my model and data file. Every time it only reads in the > second dose record and simulates based on that record. I have tried this on > three different computers running NONMEM. CLI, VI and KAI are individual > nonmem PK parameter estimates for subjects from sparse data using an > established population model setting MAXEVAL=0. I am trying to simulate a > full profile for each subject based on their PK parameters. > > $PROB SIMULATE > $INPUT C ID CMT AMT EVID TIME RATE II SS CLI VI KAI DV > > $DATA sim.csv IGNORE=C > > $SUBROUTINES ADVAN4 TRANS4 > > > $PK > > CL = CLI > V2 = VI > Q = 0.02 > V3 = 0.9 > KA = KAI > D2 = 6 > > F1=0.7 > F2=0.3 > ALAG1=0.125 > ALAG2=0.125 > > > > $ERROR CALLFL=0 > > IPRED=0 > IF(CMT.EQ.2) IPRED=LOG((A(2)+0.000001)/V2)+ERR(1) > Y = IPRED > IRES = DV - IPRED > IWRES=IRES ;W=1 for additive error model > > $OMEGA > > 0 FIXED > > $SIGMA > 0 FIXED > > $SIMULATION ONLY (12345) > > $TABLE ID TIME EVID IPRED > NOPRINT FILE=NCA > > CIDCMTAMTEVIDTIMERATEIISSCLIVIKAIDV.1110001002410.050.30.05..12100010-2241 > 0.050.30.05..12.00.01...0.050.30.05..12.00.5...0.050.30.05..12.01...0.05 > 0.30.05..12.01.5...0.050.30.05..12.02...0.050.30.05..12.02.5...0.050.30.05 > ..12.03...0.050.30.05..12.04...0.050.30.05..12.05...0.050.30.05..12.06... > 0.050.30.05..12.07...0.050.30.05..12.08...0.050.30.05..12.09...0.050.30.05 > ..12.010...0.050.30.05..12.011...0.050.30.05..12.012...0.050.30.05..12.014 > ...0.050.30.05..12.016...0.050.30.05..12.018...0.050.30.05..12.020...0.05 > 0.30.05..12.022...0.050.30.05..12.024...0.050.30.05. > > Any help would be appreciated. > > Regards, > > Justus >