Wei-jianThe error message means exactly what it says, you have, in the $MODEL record more than one compartment labeled as DEFOBS (compartments 2 and 6). Probably you don't want/need any compartment as the default dose or observation, but rather should be explicitly saying which compartment any dose/observation is associated with (likely you'll need initialization "doses" for the cells, along with drug doses, although in NM6 there are other ways to initialize the cell compartments, but if you want to do pk/cells simultaneously you'll need to make observations in two compartments). So, you'll need to add a CMT data item for doses, although in your code you do explicitly state which compartment is to be used to calculate the DV.
-------- Original Message --------
Subject: [NMusers] Simultaneous PK and Cell Life Span PD modeling
From: Wei-Jian Pan <pancooke@yahoo.com>
Date: Mon, July 16, 2007 7:14 pm
To: nmusers@globomaxnm.com
Dear group:
Perez-Ruixo and Jusko et al. published NONMEM code for
a basic cell lifespan model in 2005 (Population Cell
Life Span Models for Effects of Drugs Following
Indirect Mechanisms of Action, J Pharmacokinet
Pharmacodyn. 2005 Dec;32(5-6):767-93), which has PK
parameters modeled first, which are then used for life
span PD modeling.
I was wondering if anyone in this group has attempted
to model PK and the cell life span PD model
simultaneously. Please see followiing part of my
control streams, which yielded the error message: "167
$ MODEL: MORE THAN ONE DEFAULT COMPARTMENT FOR DOSE OR
OBSERVATION". Are there any work-arounds for this?
Many thanks!
Wei-jian
$MODEL
COMPARTMENT=(DEPOT) ; [CMT 1]
COMPARTMENT=(CENTROL, DEFOBS) ; [CMT 2]
COMPARTMENT=(PERIPH) ; [CMT 3]
COMPARTMENT=(RESPONSE) ; [CMT 4]
COMPARTMENT=(DDEPOT) ! ; [CMT 5; delay]
COMPARTMENT=(DCENTROL, DEFOBS) ; [CMT 6; delay]
COMPARTMENT=(DPERIPH) ; [CMT 7; delay]
$PK CALLFL=-2 ;Call with every event record and at
additional and lagged dose times
;DEFINE PK PARAMETERS
TVKA = THETA(1)
KA = TVKA*EXP(ETA(1))
TVCL = THETA(2)
CL = TVCL*EXP(ETA(2))
TVV2 = THETA(3)
V2 = TVV2*EXP(ETA(3))
TVQ = THETA(4)
Q = TVQ*EXP(ETA(4))
TVV3 = THETA(5)
V3 = TVV3*EXP(ETA(5))
TVF1 = THETA(6)
F1 = TVF1*EXP(ETA(6))
S2 = V2
S3 = V3
;DEFINE PD PARAMETERS
KIN = THETA(7)*EXP(ETA(7))
ALAG6 = THETA(8)*EXP(ETA(8))
ALAG5 = ALAG6
ALAG7 = ALAG6
F4 = KIN*ALAG6
EMAX = THETA(9)*EXP(ETA(9))
! IC50 = THETA(10)*EXP(ETA(10))
GAMA = THETA(11)*EXP(ET A(11))
$DES
C2 = A(2)/V2
E1 = EMAX*(C2**GAMA)/((IC50**GAMA)+(C2**GAMA))
C6 = A(6)/V2
E2 = EMAX*(C6**GAMA)/((IC50**GAMA)+(C6**GAMA))
DADT(1)=-KA*A(1)
DADT(2) = KA*A(1)-CL*A(2)/V2-Q*A(2)/V2+Q*A(3)/V3
DADT(3) = Q*A(2)/V2-Q*A(3)/V3
DADT(5) = -KA*A(5)
DADT(6) = KA*A(5)-CL*A(6)/V2-Q*A(6)/V2+Q*A(7)/V3
DADT(7) = Q*A(6)/V2-Q*A(7)/V3
DADT(4) = KIN*(1-E1) - KIN*(1-E2)
$ERROR
CP = A(2)/V2
CONC = CP*EXP(EPS(1))
EFF = A(4)*EXP(EPS(2))
Y = CONC*(1-TYPE) + EFF*TYPE
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