NONMEM Users Network Archive

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Re: Modeling Hemodialysis clearance

From: Jun Shen <jun.shen.ut>
Date: Wed, 20 Jul 2011 10:20:06 -0500

Dear Xiao,

I don't think you need an extra compartment to model the hemodialysis
clearance. I would recommend the following.

$DES

DADT(1)=-K12*A(1)
DADT(2)=K12*A(1)-K20*A(2)-Switch*KHD*A(2)

Where KHD is the hemodialysis elimination rate constant and Switch is an
data item defined in the dataset. In the dataset the Switch value is zero at
the time of start of dialysis, and 1 at the end of dialysis. Also Switch
values should be zero for all events out of dialysis sessions and 1 for all
events within dialysis.

Jun Shen
Senior Pharmacokineticist
Seventh Wave Labs

On Wed, Jul 20, 2011 at 9:26 AM, Xiao Hu <Xiao.Hu

> Dear Luann,
>
> Thanks for your advice. I realized I did not include relevant data (Excel
> change my DATE format automatically; I had to use notepad and selected the
> wrong rows). The following the updated data. PK samples were collected one
> hour before hemodialysis and one hour after hemodialysis, as well as between
> two dialysis. This may address identifiability issue. But if the system
> does not turn off Compartment 3, the identifiability will be an issue.
>
> C,ID,DATE,TIME,GROUP,CONC,AMT,MDV,TYPE,CMT,EVID
> ,102006,2010/11/11,14:35,5,0,1.25e+08,1,1,1,1
> ,102006,2010/11/11,14:35,5,0,0,1,1,-3,2
> ,102006,2010/11/11,20:35,5,44.7,0,0,1,2,0
> ,102006,2010/11/12,02:35,5,71.9,0,0,1,2,0
> ,102006,2010/11/12,14:43,5,69.8,0,0,1,2,0
> ,102006,2010/11/13,02:35,5,122,0,0,1,2,0
> ,102006,2010/11/13,14:35,5,131,0,0,1,2,0
> ,102006,2010/11/14,08:55,5,132,0,0,1,2,0
> ,102006,2010/11/14,09:00,5,0,0,1,1,3,2
> ,102006,2010/11/14,13:40,5,0,0,1,1,-3,2
> ,102006,2010/11/14,14:35,5,89.8,0,0,1,2,0
> ,102006,2010/11/15,10:29,5,68.7,0,0,1,2,0
> ,102006,2010/11/16,17:30,5,0,0,1,1,3,2
> ,102006,2010/11/16,21:30,5,0,0,1,1,-3,2
> ,102006,2010/11/18,17:40,5,0,0,1,1,3,2
> ,102006,2010/11/18,23:40,5,0,0,1,1,-3,2
> ,102006,2010/11/19,00:43,5,30,0,0,2,2,0
> ,102006,2010/11/21,16:20,5,30,0,0,2,2,0
> ,102006,2010/11/21,17:25,5,0,0,1,1,3,2
> ,102006,2010/11/21,23:25,5,0,0,1,1,-3,2
> ,102006,2010/11/23,17:40,5,0,0,1,1,3,2
> ,102006,2010/11/23,23:41,5,0,0,1,1,-3,2
> ,102006,2010/11/25,06:00,5,0,0,1,1,3,2
> ,102006,2010/11/25,10:00,5,0,0,1,1,-3,2
> ,102006,2010/11/28,12:30,5,0,0,1,1,3,2
> ,102006,2010/11/28,17:02,5,0,0,1,1,-3,2
> ,102006,2010/11/30,19:00,5,0,0,1,1,3,2
> ,102006,2010/11/30,23:55,5,0,0,1,1,-3,2
> ,102006,2010/12/02,17:55,5,0,0,1,1,3,2
> ,102006,2010/12/02,23:55,5,0,0,1,1,-3,2
> ,102006,2010/12/05,17:25,5,0,0,1,1,3,2
> ,102006,2010/12/05,20:35,5,0,0,1,1,-3,2
> ,102006,2010/12/07,18:40,5,0,0,1,1,3,2
> ,102006,2010/12/07,23:57,5,0,0,1,1,-3,2
> ,102006,2010/12/09,17:55,5,0,0,1,1,3,2
> ,102006,2010/12/09,23:55,5,0,0,1,1,-3,2
> ,102006,2010/12/16,17:48,5,0,0,1,1,3,2
> ,102006,2010/12/16,23:48,5,0,0,1,1,-3,2
> ,102007,2010/11/13,14:17,5,0,1.25e+08,1,1,1,1
> ,102007,2010/11/13,14:17,5,0,0,1,1,-3,2
> ,102007,2010/11/13,20:17,5,394,0,0,1,2,0
> ,102007,2010/11/14,02:17,5,298,0,0,1,2,0
> ,102007,2010/11/14,14:17,5,532,0,0,1,2,0
> ,102007,2010/11/15,10:22,5,615,0,0,1,2,0
> ,102007,2010/11/15,14:25,5,686,0,0,1,2,0
> ,102007,2010/11/16,07:42,5,740,0,0,1,2,0
> ,102007,2010/11/16,07:43,5,0,0,1,1,3,2
> ,102007,2010/11/16,11:48,5,0,0,1,1,-3,2
> ,102007,2010/11/16,14:17,5,703,0,0,1,2,0
> ,102007,2010/11/17,14:20,5,530,0,0,1,2,0
> ,102007,2010/11/18,10:46,5,0,0,1,1,3,2
> ,102007,2010/11/18,14:51,5,0,0,1,1,-3,2
> ,102007,2010/11/20,10:15,5,165,0,0,1,2,0
> ,102007,2010/11/20,11:22,5,0,0,1,1,3,2
> ,102007,2010/11/20,15:24,5,0,0,1,1,-3,2
> ,102007,2010/11/20,16:00,5,157,0,0,1,2,0
> ,102007,2010/11/23,09:53,5,44.7,0,0,1,2,0
> ,102007,2010/11/23,10:46,5,0,0,1,1,3,2
> ,102007,2010/11/23,14:52,5,0,0,1,1,-3,2
> ,102007,2010/11/25,10:33,5,0,0,1,1,3,2
> ,102007,2010/11/25,14:48,5,0,0,1,1,-3,2
> ,102007,2010/11/27,11:09,5,0,0,1,1,3,2
> ,102007,2010/11/27,15:01,5,0,0,1,1,-3,2
> ,102007,2010/11/30,10:59,5,30,0,0,2,2,0
> ,102007,2010/11/30,12:27,5,0,0,1,1,3,2
> ,102007,2010/11/30,15:33,5,0,0,1,1,-3,2
> ,102007,2010/12/02,12:11,5,0,0,1,1,3,2
> ,102007,2010/12/02,16:17,5,0,0,1,1,-3,2
> ,102007,2010/12/04,11:20,5,30,0,0,2,2,0
> ,102007,2010/12/04,12:18,5,0,0,1,1,3,2
> ,102007,2010/12/04,15:59,5,0,0,1,1,-3,2
> ,102007,2010/12/07,10:20,5,30,0,0,2,2,0
> ,102007,2010/12/07,11:58,5,0,0,1,1,3,2
> ,102007,2010/12/07,16:06,5,0,0,1,1,-3,2
> ,102007,2010/12/09,11:02,5,0,0,1,1,3,2
> ,102007,2010/12/09,14:33,5,0,0,1,1,-3,2
> ,102007,2010/12/12,11:44,5,30,0,0,2,2,0
> ,102007,2010/12/14,10:58,5,0,0,1,1,3,2
> ,102007,2010/12/14,15:00,5,0,0,1,1,-3,2
> ,102007,2010/12/16,11:18,5,0,0,1,1,3,2
> ,102007,2010/12/16,14:50,5,0,0,1,1,-3,2
> ,102007,2010/12/18,10:56,5,0,0,1,1,3,2
> ,102007,2010/12/18,14:56,5,0,0,1,1,-3,2
> ,104006,2010/11/12,12:30,5,0,1.25e+08,1,1,1,1
> ,104006,2010/11/12,12:30,5,0,0,1,1,-3,2
> ,104006,2010/11/12,18:30,5,100,0,0,1,2,0
> ,104006,2010/11/13,00:30,5,177,0,0,1,2,0
> ,104006,2010/11/13,12:30,5,350,0,0,1,2,0
> ,104006,2010/11/13,18:30,5,415,0,0,1,2,0
> ,104006,2010/11/15,12:30,5,362,0,0,1,2,0
> ,104006,2010/11/15,12:45,5,0,0,1,1,3,2
> ,104006,2010/11/15,16:45,5,0,0,1,1,-3,2
> ,104006,2010/11/15,17:45,5,253,0,0,1,2,0
> ,104006,2010/11/16,12:30,5,164,0,0,1,2,0
> ,104006,2010/11/17,07:40,5,0,0,1,1,3,2
> ,104006,2010/11/17,11:44,5,0,0,1,1,-3,2
> ,104006,2010/11/17,13:40,5,88.7,0,0,1,2,0
> ,104006,2010/11/19,06:05,5,47.7,0,0,1,2,0
> ,104006,2010/11/19,07:41,5,0,0,1,1,3,2
> ,104006,2010/11/19,11:45,5,0,0,1,1,-3,2
> ,104006,2010/11/19,13:06,5,31.7,0,0,1,2,0
> ,104007,2010/11/13,12:40,5,0,1.25e+08,1,1,1,1
> ,104007,2010/11/13,12:40,5,0,0,1,1,-3,2
> ,104007,2010/11/13,18:40,5,173,0,0,1,2,0
> ,104007,2010/11/14,00:40,5,234,0,0,1,2,0
> ,104007,2010/11/14,12:45,5,254,0,0,1,2,0
> ,104007,2010/11/14,18:47,5,276,0,0,1,2,0
> ,104007,2010/11/15,12:40,5,276,0,0,1,2,0
> ,104007,2010/11/16,12:40,5,332,0,0,1,2,0
> ,104007,2010/11/16,12:55,5,0,0,1,1,3,2
> ,104007,2010/11/16,16:55,5,0,0,1,1,-3,2
> ,104007,2010/11/16,17:58,5,275,0,0,1,2,0
> ,104007,2010/11/18,06:47,5,228,0,0,1,2,0
> ,104007,2010/11/18,07:52,5,0,0,1,1,3,2
> ,104007,2010/11/18,11:58,5,0,0,1,1,-3,2
> ,104007,2010/11/18,13:06,5,158,0,0,1,2,0
> ,104007,2010/11/20,06:10,5,76.3,0,0,1,2,0
> ,104007,2010/11/20,07:10,5,0,0,1,1,3,2
> ,104007,2010/11/20,11:13,5,0,0,1,1,-3,2
> ,104007,2010/11/20,11:59,5,67.1,0,0,1,2,0
> ,104010,2011/04/29,12:42,5,0,1.25e+08,1,1,1,1
> ,104010,2011/04/29,12:42,5,0,0,1,1,-3,2
> ,104010,2011/04/29,18:50,5,119,0,0,1,2,0
> ,104010,2011/04/30,00:42,5,203,0,0,1,2,0
> ,104010,2011/04/30,12:42,5,197,0,0,1,2,0
> ,104010,2011/04/30,18:42,5,295,0,0,1,2,0
> ,104010,2011/05/01,12:42,5,224,0,0,1,2,0
> ,104010,2011/05/02,12:44,5,268,0,0,1,2,0
> ,104010,2011/05/02,17:57,5,216,0,0,1,2,0
> ,104010,2011/05/04,05:40,5,161,0,0,1,2,0
> ,104010,2011/05/04,12:40,5,110,0,0,1,2,0
> ,104010,2011/05/06,03:00,5,66.7,0,0,1,2,0
> ,104010,2011/05/06,11:36,5,44.5,0,0,1,2,0
> ,106009,2011/01/28,14:15,5,0,1.25e+08,1,1,1,1
> ,106009,2011/01/28,14:15,5,0,0,1,1,-3,2
> ,106009,2011/01/28,20:15,5,52.7,0,0,1,2,0
> ,106009,2011/01/29,02:15,5,74.6,0,0,1,2,0
> ,106009,2011/01/29,14:15,5,85.2,0,0,1,2,0
> ,106009,2011/01/30,02:15,5,94.6,0,0,1,2,0
> ,106009,2011/01/30,14:15,5,102,0,0,1,2,0
> ,106009,2011/01/31,12:48,5,138,0,0,1,2,0
> ,106009,2011/01/31,13:05,5,0,0,1,1,3,2
> ,106009,2011/01/31,17:05,5,0,0,1,1,-3,2
> ,106009,2011/01/31,18:12,5,105,0,0,1,2,0
> ,106009,2011/02/02,14:07,5,118,0,0,1,2,0
> ,106009,2011/02/02,16:50,5,0,0,1,1,3,2
> ,106009,2011/02/02,20:50,5,0,0,1,1,-3,2
> ,106009,2011/02/02,22:01,5,95.1,0,0,1,2,0
> ,106009,2011/02/04,13:34,5,72.9,0,0,1,2,0
> ,106009,2011/02/04,15:54,5,0,0,1,1,3,2
> ,106009,2011/02/04,20:06,5,0,0,1,1,-3,2
> ,106009,2011/02/04,21:18,5,60.3,0,0,1,2,0
> ,106009,2011/02/07,00:50,5,0,0,1,1,-3,2
> ,106009,2011/02/07,11:02,5,39.4,0,0,1,2,0
> ,106009,2011/02/07,17:20,5,0,0,1,1,3,2
> ,106009,2011/02/09,01:05,5,0,0,1,1,-3,2
> ,106009,2011/02/09,17:05,5,0,0,1,1,3,2
> ,106009,2011/02/11,01:23,5,0,0,1,1,-3,2
> ,106009,2011/02/11,08:49,5,30,0,0,2,2,0
> ,106009,2011/02/11,17:15,5,0,0,1,1,3,2
> ,106009,2011/02/14,01:17,5,0,0,1,1,-3,2
> ,106009,2011/02/14,08:44,5,30,0,0,2,2,0
> ,106009,2011/02/14,17:17,5,0,0,1,1,3,2
> ,106009,2011/02/16,01:20,5,0,0,1,1,-3,2
> ,106009,2011/02/16,17:20,5,0,0,1,1,3,2
> ,106009,2011/02/18,01:08,5,0,0,1,1,-3,2
> ,106009,2011/02/18,17:02,5,0,0,1,1,3,2
> ,106009,2011/02/21,01:04,5,0,0,1,1,-3,2
> ,106009,2011/02/21,17:04,5,0,0,1,1,3,2
> ,106009,2011/02/23,17:39,5,0,0,1,1,3,2
> ,106009,2011/02/23,21:45,5,0,0,1,1,-3,2
> ,106009,2011/02/25,16:55,5,0,0,1,1,3,2
> ,106009,2011/02/25,20:56,5,0,0,1,1,-3,2
> ,106009,2011/02/28,01:06,5,0,0,1,1,-3,2
> ,106009,2011/02/28,17:21,5,0,0,1,1,3,2
> ,106009,2011/03/02,01:01,5,0,0,1,1,-3,2
> ,106009,2011/03/02,17:05,5,0,0,1,1,3,2
> -----Original Message-----
> From: Luann Phillips [mailto:Luann.Phillips
> Sent: Wednesday, July 20, 2011 9:45 AM
> To: Xiao Hu
> Cc: nmusers
> Subject: Re: [NMusers] Modeling Hemodialysis clearance
>
> 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,
> >
> >
> >
> > I'm 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. I'm wondering if you can point me to the right direction. I'd
> 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
> >
>
>
> > ,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 - 11:20:06 EDT

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