Re: 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 > > 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