Re: Modeling Hemodialysis clearance
Dear Xiao,
I agree with Jun's advise. You previous setting should not work as
when you switch the compartment 3 off nothing changes for
compartment 2, k23 stays the same as it was.
Regards,
Katya
Ekaterina Gibiansky, Ph.D.
CEO&CSO, QuantPharm LLC
Web: www.quantpharm.com
Email: [email protected]
Tel: (301)-717-7032
On 7/20/2011 11:20 AM, Jun Shen wrote:
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
< [email protected] >
wrote:
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-----
Quoted reply history
From: Luann Phillips [mailto: [email protected] ]
Sent: Wednesday, July 20, 2011 9:45 AM
To: Xiao Hu
Cc: [email protected]
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
>