RE: Simultaneous PK and Cell Life Span PD modeling
Wei-jian
The error message means exactly what it says, you have, in the $MODEL record more than one compartment labeled as DEFOBS (compartments 2 and 6). Probably you don't want/need any compartment as the default dose or observation, but rather should be explicitly saying which compartment any dose/observation is associated with (likely you'll need initialization "doses" for the cells, along with drug doses, although in NM6 there are other ways to initialize the cell compartments, but if you want to do pk/cells simultaneously you'll need to make observations in two compartments). So, you'll need to add a CMT data item for doses, although in your code you do explicitly state which compartment is to be used to calculate the DV. Mark Sale MD Next Level Solutions, LLC
www.NextLevelSolns.com
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-------- Original Message --------
Subject: [NMusers] Simultaneous PK and Cell Life Span PD modeling
From: Wei-Jian Pan <[EMAIL PROTECTED]>
Date: Mon, July 16, 2007 7:14 pm
To: [email protected]
Dear group:Perez-Ruixo and Jusko et al. published NONMEM code fora basic cell lifespan model in 2005 (Population CellLife Span Models for Effects of Drugs FollowingIndirect Mechanisms of Action, J PharmacokinetPharmacodyn. 2005 Dec;32(5-6):767-93), which has PKparameters modeled first, which are then used for lifespan PD modeling.I was wondering if anyone in this group has attemptedto model PK and the cell life span PD modelsimultaneously. Please see followiing part of mycontrol streams, which yielded the error message: "167$ MODEL: MORE THAN ONE DEFAULT COMPARTMENT FOR DOSE OROBSERVATION". 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 atadditional 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 ____________________________________________________________________________________Boardwalk for $500? In 2007? Ha! Play Monopoly Here and Now (it'supdated for today's economy) at Yahoo! Games. http://get.games.yahoo.com/proddesc?gamekey=monopolyherenow