Eileen,
I am not sure why, it is hard to say without seeing the data. Why do you fix some parameters? let them go free. Also, I would put ETA on V1 rather than on KM. Try to add all etas to get the good fit, and only then reduce the model.
I see your units of CL as L/kg. It looks like you use mg/kg dose rather than the true dose. I would rather recommend to work in real (not WT-normalized) variables, and add WT to the parameters as needed (like allometric scaling).
Also, TOL=5 is too low, try TOL=9.
If you have problem posting to the group, ask ICON to check your address: you should post messages from the address registered in the list. If you changed the address, it needs to be reflected on the server. I copied the nmusers, this reply will appear on the list.
Regards,
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 4/11/2012 3:05 PM, Eileen Lawson wrote:
> Leonid,
>
> I tried to post this to the NM Users list, but for some reason I cannot
> post directly so:
>
> Good afternoon,
>
> I'm working on an antibody model with parallel linear and nonlinear
> elimination from the central compartment. The model predicts only to 100
> mg/L, even though the DV reaches 150 mg/L. For all DV > 100 mg/L, the
> model predicts 100 mg/L. Can you suggest where I might be mis-specifying
> to get this result?
>
> Thank you,
> Eileen
>
> $SUBROUTINE ADVAN13 TOL=5
>
> $MODEL
> NCOMP = 2
> COMP = (CENTRAL) ;1
> COMP = (PERIPH) ;2
>
> $PK
> CL = THETA(1) * EXP(ETA(1))
> V1 = THETA(2)
> Q = THETA(3)
> V2 = THETA(4)
> VM = THETA(5) * EXP(ETA(2))
> KM = THETA(6) * EXP(ETA(3))
>
> S1 = V1
> S2 = V2
> K10 = CL/V1
> K12 = Q/V1
> K21 = Q/V2
>
> $ERROR
> TY = A(1)/V1
> IPRED = TY
> W = SQRT(THETA(7)**2/TY**2+THETA(8)**2)
> Y = IPRED*EXP(W*ERR(1))
>
> $DES
> C1 = A(1)/S1
> DADT(1) = -K10*A(1)-A(1)*VM/ (KM+C1)-K12*A(1)+K21*A(2)
> DADT(2) = K12*A(1)-K21*A(2)
>
> $THETA
> (0, 0.003) ; CL, L/kg
> 0.044 FIX ; V1, L/kg
> (0, 0.00002) ; Q (RAPID), L/day/kg
> 0.0177 FIX ; V2, L/kg
> (0, 0.00004) ; VM (CLSAT), mg/day/kg
> (0, 0.025) ; KM , mg/L/kg
> (0, 0.19) ; proportional error
> (0, 0.2) ; additive error
>
> $OMEGA
> (0.09) ; 30% VARIANCE IN CL
> 0.0225 FIX ; 15% VARIANCE IN VM
> 0.0225 FIX ; 15% VARIANCE in KM