Modeling Hemodialysis clearance
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
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