How to set CMT value for 2-compartment bacterial model

-----Original Message----- From: [email protected] [mailto:[email protected]] On Behalf Of Sherwin K Sy Sent: Friday, January 06, 2012 10:59 PM To: [email protected] Subject: [NMusers] How to set CMT value for 2-compartment bacterial model Dear NONMEM users, I want to set-up a bacterial model consisting of susceptible (S) and resting phases (R). I use Advan9 in NONMEM for the subroutine. With Advan9, one has to declare compartments. My experimental bacterial counts belong to both S and R (i.e. sum of S and R). And the compartments are such that: CA=(A(3)) ; compartment for drug DRUG=EMAX*(CA)/(EC50+(CA)) ; relationship for drug using an Emax model DADT(1)=K1*A(1)-(K2+DRUG)*A(1)-KSR*A(1) DADT(2)=KSR*A(1)-K2*A(2) DADT(3)=KDEG*A(3) A1=A(1) ; S A2=A(2) ; R ATOT=A1+A2 ; N=S+R A3=A(3) ; Drug Concentration IPRED = ATOT I'm wondering as to how or what to set-up for the compartment value CMT in the input file whenever I have bacterial count observations. I understand that the CMT for the initial drug concentration will be set to 3 since drug belongs to compartment 3. Thank you in advance for your help. Best regards, Sherwin Sy

On 10/01/2012 9:50 a.m., Elisabet Nielsen wrote: > Dear Sherwin, > > Since you have specified IPRED=ATOT (and ATOT=A1+A2), NONMEM is disregarding > the CMT value you have specified on the observation record when calculating > IPRED, i.e. you can set CMT to any value. > > Best regards, > > Elisabet > > ---------------------------------------------------------------- > Elisabet Nielsen, PhD > The Pharmacometrics group > Department of Pharmaceutical Biosciences > Uppsala University > > -----Original Message----- > From: [email protected] [mailto:[email protected]] On > Behalf Of Sherwin K Sy > Sent: Friday, January 06, 2012 10:59 PM > To: [email protected] > Subject: [NMusers] How to set CMT value for 2-compartment bacterial model > > Dear NONMEM users, > > I want to set-up a bacterial model consisting of susceptible (S) and > resting phases (R). I use Advan9 in NONMEM for the subroutine. With > Advan9, one has to declare compartments. > > My experimental bacterial counts belong to both S and R (i.e. sum of S > and R). And the compartments are such that: > > CA=(A(3)) ; compartment for drug > > DRUG=EMAX*(CA)/(EC50+(CA)) ; relationship for drug using an Emax model > > DADT(1)=K1*A(1)-(K2+DRUG)*A(1)-KSR*A(1) > DADT(2)=KSR*A(1)-K2*A(2) > DADT(3)=KDEG*A(3) > > A1=A(1) ; S > A2=A(2) ; R > ATOT=A1+A2 ; N=S+R > A3=A(3) ; Drug Concentration > > IPRED = ATOT > > I'm wondering as to how or what to set-up for the compartment value > CMT in the input file whenever I have bacterial count observations. I > understand that the CMT for the initial drug concentration will be set > to 3 since drug belongs to compartment 3. > > Thank you in advance for your help. > > Best regards, > > Sherwin Sy -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology& Clinical Pharmacology, Bldg 505 Room 202D University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

On Mon, Jan 9, 2012 at 4:14 PM, Nick Holford <[email protected]> wrote: > Hi, > > Just to expand on this topic a little. > > I only use the CMT data item to specify the compartment when AMT is > 0 and > the default CMT=1 is not appropriate (or when I need to turn off/turn on a > compartment). Otherwise I don't use CMT or set CMT to "." (which NM-TRAN > translates to 0 for NONMEM) for all observation records. The CMT data item > does not directly affect the prediction of any observation. > > When I have different kinds of observations (e.g. parent, metabolite or > conc, effect) then I include a DVID data item in the data set to determine > which prediction ('Y') should be used. Some people use CMT for this but this > can cause problems e.g. if you have only 1 PK compartment and a conc and 2 > effects to predict then you cannot use CMT to choose which effect should be > used for the prediction. > > e.g. here is an example that does not use CMT explicitly (it is 1 by default > for AMT>0) but uses DVID to determine the prediction. > > $INPUT ID TIME AMT DV DVID > $SUBR ADVAN1 > $ERROR > IF (DVID.EQ.1) THEN > Y=CONC + EPS(1) > ENDIF > IF (DVID.EQ.2) THEN > Y=EFFECT1+ EPS(2) > ENDIF > IF (DVID.EQ.3) THEN > Y=EFFECT2+ EPS(3) > ENDIF > > > On 10/01/2012 9:50 a.m., Elisabet Nielsen wrote: >> >> Dear Sherwin, >> >> Since you have specified IPRED=ATOT (and ATOT=A1+A2), NONMEM is >> disregarding >> the CMT value you have specified on the observation record when >> calculating >> IPRED, i.e. you can set CMT to any value. >> >> Best regards, >> >> Elisabet >> >> ---------------------------------------------------------------- >> Elisabet Nielsen, PhD >> The Pharmacometrics group >> Department of Pharmaceutical Biosciences >> Uppsala University >> >> >> -----Original Message----- >> From: [email protected] [mailto:[email protected]] >> On >> Behalf Of Sherwin K Sy >> Sent: Friday, January 06, 2012 10:59 PM >> To: [email protected] >> Subject: [NMusers] How to set CMT value for 2-compartment bacterial model >> >> Dear NONMEM users, >> >> I want to set-up a bacterial model consisting of susceptible (S) and >> resting phases (R). I use Advan9 in NONMEM for the subroutine. With >> Advan9, one has to declare compartments. >> >> My experimental bacterial counts belong to both S and R (i.e. sum of S >> and R). And the compartments are such that: >> >> CA=(A(3)) ; compartment for drug >> >> DRUG=EMAX*(CA)/(EC50+(CA)) ; relationship for drug using an Emax model >> >> DADT(1)=K1*A(1)-(K2+DRUG)*A(1)-KSR*A(1) >> DADT(2)=KSR*A(1)-K2*A(2) >> DADT(3)=KDEG*A(3) >> >> A1=A(1) ; S >> A2=A(2) ; R >> ATOT=A1+A2 ; N=S+R >> A3=A(3) ; Drug Concentration >> >> IPRED = ATOT >> >> I'm wondering as to how or what to set-up for the compartment value >> CMT in the input file whenever I have bacterial count observations. I >> understand that the CMT for the initial drug concentration will be set >> to 3 since drug belongs to compartment 3. >> >> Thank you in advance for your help. >> >> Best regards, >> >> Sherwin Sy >> > > -- > Nick Holford, Professor Clinical Pharmacology > Dept Pharmacology& Clinical Pharmacology, Bldg 505 Room 202D > University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand > tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 > email: [email protected] > http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford >