[NMusers] Simultaneous PK and Cell Life Span PD modeling

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(ETA(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's updated for today's economy) at Yahoo! Games.
http://get.games.yahoo.com/proddesc?gamekey=monopolyherenow
Received on Mon Jul 16 2007 - 19:14:48 EDT