Dear Ann,
Change to ALAG4. Note that you could use ADVAN 5 or 7 for this model if you specify all rate constants. These should be faster. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Sweden Postal address: Box 591, 751 24 Uppsala, Sweden Phone +46 18 4714105 Fax + 46 18 4714003 From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Ann Rigby-Jones Sent: Friday, August 06, 2010 11:46 AM To: 'nmusers@globomaxnm.com' Subject: [NMusers] ALAG with transit model Dear NMUsers I'm trying to evaluate a transit model in an attempt to better describe early drug concentrations following intravenous injection (1 minute and 10 minute infusions) of a sedative-hypnotic drug. Additionally, I have incorporated lag times to described the short delay between the infusion pump being turned on and the drug emerging from the cannula. This time delay differed between the 1min and 10 min infusion groups due to differences in the pump flow rate. When I model using a classic 3 or 4-compartment mamillary model, ALAG is estimated and models minimise successfully. However, when I try to incorporate transit compartments, ALAG is not estimated (THETAs remain as the initial estimate). There must be something wrong with my control stream but I'm struggling to spot the problem, grateful for any thoughts! I'm using NONMEM7 and PLT Tools. With thanks and all best wishes Ann $PROBLEM 3comp 3 transit advan9 $INPUT ID DOSE AMT RATE DUR TIME ORI DV EVID ART AGE WGT $DATA PKcen12LN.csv IGNORE=# $SUBROUTINES ADVAN9 TOL=3 $MODEL ;NCOMPS=9 COMP(CENTRAL, DEFOBS) ;1 COMP(PERIPH1) ;2 COMP(PERIPH2) ;3 COMP(TRANS1, DEFDOSE) ;4 COMP(TRANS2) ;5 COMP(TRANS3) ;6 ;COMP(TRANS4) ;7 ;COMP(TRANS5) ;8 ;COMP(TRANS6) ;9 $PK CL=THETA(1)*EXP(ETA(1)) Q2=THETA(2)*EXP(ETA(2)) Q3=THETA(3)*EXP(ETA(3)) V1=THETA(4)*EXP(ETA(4)) V2=THETA(5)*EXP(ETA(5)) V3=THETA(6)*EXP(ETA(6)) K10=CL/V1 K12=Q2/V1 K13=Q3/V1 K21=Q2/V2 K31=Q3/V3 IF (DUR.EQ.10) THEN ALAG1=THETA(7)*EXP(ETA(7)) ELSE ALAG1=THETA(8)*EXP(ETA(7)) ENDIF KTR=THETA(9)*EXP(ETA(8)) S1=V1 $DES ;standard 3-comp model ;DADT(1)=A(2)*K21 + A(3)*K31 - A(1)*(K10+K12+K13) ;DADT(2)=A(1)*K12 - A(2)*K21 ;DADT(3)=A(1)*K13 - A(3)*K31 ;3 comp transit model DADT(1)=A(6)*KTR + A(2)*K21 + A(3)*K31 - A(1)*(K10+K12+K13) DADT(2)=A(1)*K12 - A(2)*K21 DADT(3)=A(1)*K13 - A(3)*K31 DADT(4)=-A(4)*KTR DADT(5)=A(4)*KTR - A(5)*KTR DADT(6)=A(5)*KTR - A(6)*KTR ;DADT(7)=A(6)*KTR - A(7)*KTR ;DADT(8)=A(7)*KTR - A(8)*KTR ;DADT(9)=A(8)*KTR - A(9)*KTR $ERROR W=1 IPRED= -2 IF (F.GT.0) IPRED=LOG(F) Y=IPRED + ERR(1) IRES=DV-IPRED IWRES=IRES/W $THETA (0, 563) ;CL $THETA (0, 336) ;Q2 $THETA (0, 2640) ;Q3 $THETA (0, 2630) ;V1 $THETA (0, 41200) ;V2 $THETA (0, 27600) ;V3 $THETA (0.2167, 0.549,1) ;ALAG 10MIN $THETA (0.00833, 0.101, 1) ;ALAG 1MIN $THETA (0, 0.282) ;KTR $OMEGA (0.0456) ; ETA CL $OMEGA (1.37) ; ETA Q2 $OMEGA (0.133) ; ETA Q3 $OMEGA (0 FIX) ; ETA V1 $OMEGA (0.405) ; ETA V2 $OMEGA (0 FIX) ; ETA V3 $OMEGA (0. 2) ; ETA LAG SHARED $OMEGA (0.33) ; ETA KTR $SIGMA (0.570) $ESTIMATION METHOD=1 PRINT=1 MAX=9999 NOABORT SIG=3 ;POSTHOC INTER MSFO=msfo.outputfile $COVA $TABLE ID EVID AMT TIME IPRED IRES NOPRINT FILE=AllRecords.txt $TABLE ID CL Q2 Q3 V1 V2 V3 ETA1 ETA2 ETA3 ETA4 ETA5 ETA6 ETA7 ;ETA8 FIRSTONLY NOPRINT NOAPPEND FILE=FirstRecords.txt ______________________________________________________________________ Ann Rigby-Jones PhD MRSC Research Fellow in Pharmacokinetics & Pharmacodynamics Peninsula College of Medicine & Dentistry N31, ITTC Phase 1 Tamar Science Park 1 Davy Road Derriford Plymouth PL6 8BX _______________________________________________________________________
