NONMEM Users Network Archive

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Re: Modeling Hemodialysis clearance

From: Luann Phillips <Luann.Phillips>
Date: Wed, 20 Jul 2011 09:44:42 -0400

Xiao Hu,

I think it may be a problem with identifiability. It can't separate the
definition of K23 from K20 unless there are measurements during
elimination for hemo. patients off dialysis and on dialysis.

Thoughts:
(1) Try making K20=0 for hemodialysis patients
Assumes: no elimination except during hemodialysis via K23
(2) Estimate a different theta for K20 in hemodialysis patients since it
should be different for them (bi-modal distribution)
Assumes: very small elimination from central & with additive elimination
from hemodialysis via K23.

Regards,

Luann Phillips
Director, PK/PD
Cognigen Corporation

Xiao Hu wrote:
> Dear NM users,
>
>
>
> Im working on a PK model in renal disease patients with hemodialysis.
> The drug in healthy subjects is well described with a first-order
> absorption and one-compartment disposition model. A third hemodialysis
> compartment was added; CMT=3 or -3 were included in the data set to turn
> this compartment on and off. However, the 3rd compartment did not seem
> to be turned off, based on the fact that the same results were obtained
> whether I excluded the EVID==2 record or not (corresponding to CMT==3 or
> -3). Both ADVAN6 and ADVAN7 provided the same results as well. The
> code and partial data set are shown below. Im wondering if you can
> point me to the right direction. Id really appreciate your input. Thanks!
>
>
>
> Best regards,
>
> Xiao
>
>
>
> $INPUT C ID DAT2=DROP TIME GROUP DV AMT MDV TYPE CMT EVID
>
>
>
> $DATA .\DATA\FINAL\105RI101ESRDPK.CSV
>
> IGNORE=C IGN(GROUP.NE.5) ;IGN(EVID.EQ.2)
>
>
>
> $SUBROUTINES ADVAN7 ;ADVAN6 TOL=8
>
>
>
> $MODEL
>
> COMP=(DEPOT,INITIALOFF,DEFDOSE)
>
> COMP=(CENTRAL,DEFOBS,NOOFF)
>
> COMP=(HEMODIA,INITIALOFF)
>
>
>
> $PK
>
> K12=THETA(1)
>
> K20=THETA(2)
>
> K23=THETA(3)
>
> K32=0
>
> V2=THETA(4)*EXP(ETA(1))
>
> S2=V2
>
> $ERROR
>
> Y=F*EXP(EPS(1))
>
> IPRE=F
>
>
>
> ;$DES
>
> ;DADT(1)=-K12*A(1)
>
> ;DADT(2)=K12*A(1)-K23*A(2)-K20*A(2)
>
> ;DADT(3)=K23*A(2)
>
>
>
> $THETA
>
> (0,0.1) ;THETA1 K12
>
> (0,0.05) ;THETA2 K20
>
> (0,.102) ;THETA3 K23
>
> (0,200000) ;THETA6 V2
>
>
>
> $OMEGA
>
> 0.2
>
> $SIGMA
>
> 0.2
>
>
>
> $ESTIMATION MAXEVAL=9999 METH=COND PRINT=5 MSFO=ESRD.MSF FILE=ESRD.EXT
>
> C,ID,DATE,TIME,GROUP,CONC,AMT,MDV,TYPE,CMT,EVID
>
> ,102001,2010/05/04,8:35,2,0,6.3e+07,1,1,1,1
>
> ,102001,2010/05/04,8:35,2,0,0,1,1,-3,2
>
> ,102001,2010/05/04,14:39,2,177,0,0,1,2,0
>
> ,102001,2010/05/04,20:35,2,190,0,0,1,2,0
>
> ,102001,2010/05/05,08:35,2,144,0,0,1,2,0
>
> ,102001,2010/05/05,20:35,2,145,0,0,1,2,0
>
> ,102001,2010/05/06,08:37,2,135,0,0,1,2,0
>
> ,102001,2010/05/07,08:41,2,139,0,0,1,2,0
>
> ,102001,2010/05/08,08:35,2,177,0,0,1,2,0
>
> ,102001,2010/05/11,08:35,2,82.2,0,0,1,2,0
>
> ,102002,2010/06/30,8:00,2,0,1.25e+08,1,1,1,1
>
> ,102002,2010/06/30,8:00,2,0,0,1,1,-3,2
>
> ,102002,2010/06/30,14:03,2,416,0,0,1,2,0
>
> ,102002,2010/06/30,21:00,2,727,0,0,1,2,0
>
> ,102002,2010/07/01,08:21,2,1040,0,0,1,2,0
>
> ,102002,2010/07/01,20:00,2,1070,0,0,1,2,0
>
> ,102002,2010/07/02,08:06,2,719,0,0,1,2,0
>
> ,102002,2010/07/03,08:00,2,580,0,0,1,2,0
>
> ,102002,2010/07/04,08:00,2,518,0,0,1,2,0
>
> ,102002,2010/07/07,08:00,2,127,0,0,1,2,0
>
> ,102002,2010/07/10,08:00,2,35.2,0,0,1,2,0
>
> ,102002,2010/07/14,08:08,2,30,0,0,2,2,0
>
> ,102002,2010/07/17,08:00,2,30,0,0,2,2,0
>
> ,102002,2010/07/21,08:00,2,30,0,0,2,2,0
>
> ,102002,2010/07/23,15:05,2,30,0,0,2,2,0
>
> ,102002,2010/07/28,08:21,2,30,0,0,2,2,0
>
> ,102003,2010/08/06,8:35,3,0,1.25e+08,1,1,1,1
>
> ,102003,2010/08/06,8:35,3,0,0,1,1,-3,2
>
> ,102003,2010/08/06,14:35,3,132,0,0,1,2,0
>
> ,102003,2010/08/06,20:35,3,189,0,0,1,2,0
>
> ,102003,2010/08/07,08:35,3,210,0,0,1,2,0
>
> ,102003,2010/08/07,20:35,3,246,0,0,1,2,0
>
> ,102003,2010/08/08,08:35,3,221,0,0,1,2,0
>
> ,102003,2010/08/09,08:35,3,236,0,0,1,2,0
>
> ,102003,2010/08/10,08:35,3,180,0,0,1,2,0
>
> ,102003,2010/08/13,08:35,3,55.9,0,0,1,2,0
>
> ,102004,2010/08/31,7:40,3,0,1.25e+08,1,1,1,1
>
> ,102004,2010/08/31,7:40,3,0,0,1,1,-3,2
>
> ,102004,2010/08/31,13:52,3,309,0,0,1,2,0
>
> ,102004,2010/08/31,19:40,3,252,0,0,1,2,0
>
> ,102004,2010/09/01,07:40,3,224,0,0,1,2,0
>
> ,102004,2010/09/01,19:43,3,265,0,0,1,2,0
>
> ,102004,2010/09/02,07:40,3,306,0,0,1,2,0
>
> ,102004,2010/09/03,07:40,3,328,0,0,1,2,0
>
> ,102004,2010/09/04,07:40,3,206,0,0,1,2,0
>
> ,102004,2010/09/07,07:40,3,37.6,0,0,1,2,0
>
Received on Wed Jul 20 2011 - 09:44:42 EDT

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