Hi Wei-jian, I let others help you with the NONMEM coding. However, I would like to ask what type of data set you have. It seems that you have such a rich data set for both PK and PD observations that allows you to estimate a total of 14 different parameters, including 11 associated with variability of every single structural model parameter. Is it really reasonable to, e.g., expect your plasma concentration data to provide reliable estimates of both structural model parameters of a 2-comp model with an absorption component as well as the variability terms associated with every single parameter of the model?
I would suggest that you start with the simplest model you believe is reasonable in reflecting the underlying mechanism of the plasma concentration and effect data and include a single ETA to start with. Once you have the structural model in place, you could explore the possibility of estimating the variability terms with the model parameters. This approach should allow you to get the PK/PD model in place early on, with much shortened computing time. Toufigh -----Original Message----- From: [EMAIL PROTECTED] on behalf of Wei-Jian Pan Sent: Mon 7/16/2007 4:14 PM To: [email protected] Subject: [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
