Dear Donna,
For the second MTIME, the correct use of MPAST should be: MU_8=LOG(THETA(8)*(MPAST(1)-MPAST(2))+THETA(10)*MPAST(2)) I was wondering, however, if the absorption rate constants for the single and multiple doses are believed to be different as well as before and after the MTIME. If not, I think using one MTIME as follows might allow the MTIME(1) to be applied for both single and multiple doses (this is just a suggestion; not tested). $PK CALLFL=-2 IF (NEWIND.LT.2) THEN RTM=0 ENDIF IF (EVID.GE.1) RTM=TIME IF (DOSTIM.NE.0) RTM=DOSTIM ;IF(TIME.LE.24)THEN MU_5=LOG(THETA(5)) MTIME(1)=EXP(MU_5+ETA(5)) +RTM MU_6=LOG(THETA(6)*(1-MPAST(1))+THETA(9)*MPAST(1)) KA=EXP(MU_6+ETA(6)) ;ENDIF ;IF(TIME.GT.24)THEN ;MU_7=LOG(THETA(7)) ;MTIME(2)=EXP(MU_7+ETA(7)) ;MU_8=LOG(THETA(8)*(1-MPAST(1))+THETA(10)*MPAST(1)) ;KA=EXP(MU_8+ETA(8)) ;ENDIF MTDIFF=1 Thanks, Jae Eun ________________________________ From: [email protected] [mailto:[email protected]] On Behalf Of Donna Cox Sent: Wednesday, July 14, 2010 9:50 AM To: Elassaiss - Schaap, J. (Jeroen); [email protected] Subject: RE: [NMusers] MTIME for both Single and Repeat Dose PK in NONMEM VII HI Jeroen- Thanks for your response! My data follows a 2-com model. The data set I have coded in ADDL and II (trying to avoid SS records). I have specified MTIME(1) by time <24 hours (Day 1) and MTIME (2) by time >24 hours (Day 15). I have included some code below to be more specific. Thanks Donna $PROBLEM MEK FTIH POPULATION PK MODELING $INPUT C ID TIME CP DV AMT=DOSE WT EVID DAY ADDL II BMI $DATA MEKALL1.CSV IGNORE=C $SUBROUTINES ADVAN4 TRANS4 $PK TVCL=THETA(1) MU_1=LOG(TVCL) CL=EXP(MU_1+ETA(1)) TVV2=THETA(2) MU_2=LOG(TVV2) V2=EXP(MU_2+ETA(2)) TVV3=THETA(3) MU_3=LOG(TVV3) V3=EXP(MU_3+ETA(3)) TVQ=THETA(4) MU_4=LOG(TVQ) Q=EXP(MU_4+ETA(4)) IF(TIME.LE.24)THEN MU_5=LOG(THETA(5)) MTIME(1)=EXP(MU_5+ETA(5)) MU_6=LOG(THETA(6)*(1-MPAST(1))+THETA(9)*MPAST(1)) KA=EXP(MU_6+ETA(6)) ENDIF IF(TIME.GT.24)THEN MU_7=LOG(THETA(7)) MTIME(2)=EXP(MU_7+ETA(7)) MU_8=LOG(THETA(8)*(1-MPAST(1))+THETA(10)*MPAST(1)) KA=EXP(MU_8+ETA(8)) ENDIF MTDIFF=1 S2=V2 From: Elassaiss - Schaap, J. (Jeroen) [mailto:[email protected]] Sent: Wednesday, July 14, 2010 9:38 AM To: Donna Cox; [email protected] Subject: RE: [NMusers] MTIME for both Single and Repeat Dose PK in NONMEM VII Hi Donna, Could you please provide additional details, i.e. core model code (dataset layout and crash message)? You may need to specify the MTIMEs for each dose given to the system which may not be practical. This may be an opportunity for future nonmem versions, to be able to specify MTIMEs relative to the active dose in the system. Perhaps not feasible for SS records. Best regards, Jeroen Modeling & Simulation Expert Pharmacokinetics, Pharmacodynamics & Pharmacometrics (P3) - DMPK MSD PO Box 20 - AP1112 5340 BH Oss The Netherlands [email protected] T: +31 (0)412 66 9320 M: +31 (0)6 46 101 283 F: +31 (0)412 66 2506 www.msd.com ________________________________ From: [email protected] [mailto:[email protected]] On Behalf Of Donna Cox Sent: Wednesday, 14 July, 2010 14:17 To: [email protected] Subject: [NMusers] MTIME for both Single and Repeat Dose PK in NONMEM VII Hi All: I have a combined single and repeat dose data set that I am trying to model in NONMEM VII. I can model the single dose data with MTIME successfully (tremendous improvement in fit compared to 2-COM model without MTIME). Does anyone have any experience modeling BOTH single and repeat dose data with MTIME?? I have tried using 2 MTIME's (one for single and one for the repeat dose data, but it crashes). Any suggestions would be helpful. Thanks much Donna Donna S. Cox, PhD GlaxoSmithKline Quantitative Sciences Clinical Pharmacology Modeling and Simulation UM 24-3059 King of Prussia, Philadelphia 610-270-4395 ________________________________ This message and any attachments are solely for the intended recipient. If you are not the intended recipient, disclosure, copying, use or distribution of the information included in this message is prohibited --- Please immediately and permanently delete. ________________________________
