Re: Modeling Hemodialysis clearance

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----- > 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 > > > >