RE: [NMusers] MTIME for both Single and Repeat Dose PK in NONMEM VII

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: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com]
On Behalf Of Donna Cox
Sent: Wednesday, July 14, 2010 9:50 AM
To: Elassaiss - Schaap, J. (Jeroen); nmusers_at_globomaxnm.com
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:jeroen.elassaiss_at_spcorp.com]
Sent: Wednesday, July 14, 2010 9:38 AM
To: Donna Cox; nmusers_at_globomaxnm.com
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
jeroen.elassaiss_at_merck.com
T: +31 (0)412 66 9320
M: +31 (0)6 46 101 283
F: +31 (0)412 66 2506
www.msd.com

 

________________________________

From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com]
On Behalf Of Donna Cox
Sent: Wednesday, 14 July, 2010 14:17
To: nmusers_at_globomaxnm.com
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

 

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Received on Wed Jul 14 2010 - 12:32:49 EDT