Request for help about M-M kinetics
From: "Honghui Zhou" HZHOU@janwcc1.ssw.jnj.com
Subject: Request for help about M-M kinetics
Date: 17 Sep 1997 12:18:34 -0400
Dear NONMEM user friends
My name is Honghui Zhou. I am now working at Janssen Pharmaceutica, Dept. of Clinical Pharmacokinetics as a Scientist. I am trying to establish a two-compartment model with first order input and M-M output. The command stream is listed below. When I run it, the message I got is MINIMIZATION SUCCESSFUL, but the PRED values are 10,000 times less than the DV. I tried very hard, but the problem still exists. Maybe something wrong with the scale factor. Because I used differential equations in the command file, how can I use a appropriate scaling factor. Or there is other problem with my command file. I would appreciate if you could help me out.
Since we can not send out the attached files outside the company, I have to copy the command file & data file (only one subject) below. Sorry for the inconvenience. The dose is 200 mg, while the unit for DV is ng/mL. The drug was administered BID for 15 days, on Day 15, a whole plasma profile was captured.
Thank you very much in advance for your kind help. I am looking forward to your response.
Best regards,
Honghui Zhou, Ph.D.
Janssen Research Foundation
(609) 730-3011 (phone)
(609) 730-3044 (fax)
e-mail: hzhou@janus.jnj.com
$PROB ITR Nonlinear Kinetics Modeling $INPUT ID TIME AMT DV
$DATA 916.PRN
$SUBROUTINES ADVAN6 TRANS1 TOL=4
$MODEL COMP=(DEPOT,DEFDOS) COMP=(CENTRAL,DEFOBS) COMP=(PERIPH) $PK
VM=THETA(1)
KM=THETA(2)
K12=THETA(3)
K23=THETA(4)
K32=THETA(5)
S2=THETA(6)
$ERROR
Y=F+ERR(1)
$DES
C2=A(2)/S2
DADT(1)=-K12*A(1)
DADT(2)=-K12*A(1)-K23*A(2)+K32*A(3)-C2*VM/(KM+C2)
DADT(3)=K23*A(2)-K32*A(3)
$THETA
(0, 9, 1000)
(0, 330, 1000)
(0, 0.5, 10)
(0, 0.2, 10)
(0, 0.07, 10)
(0, 800, 5000)
$OMEGA 1.2
$EST SIG=5 MAXEVAL=9999 NOABORT PRINT=5 $COVARIANCE
$TABLE TIME DV VM KM K12 K23 K32
FILE=918a.out
$SCATTER PRED VS DV UNIT
1 0 200000 0
1 12 200000 0
1 24 200000 0
1 36 200000 0
1 48 200000 0
1 72 200000 0
1 96 200000 0
1 108 200000 0
1 120 200000 0
1 132 200000 0
1 144 200000 0
1 156 200000 0
1 168 200000 0
1 180 200000 0
1 192 200000 0
1 204 200000 0
1 216 200000 0
1 228 200000 0
1 240 200000 0
1 252 200000 0
1 264 200000 0
1 276 200000 0
1 288 200000 0
1 300 200000 0
1 312 200000 0
1 324 200000 0
1 336 200000 0
1 348 200000 0
1 360 200000 0
1 360.5 0 407
1 361 0 564
1 362 0 820
1 363 0 990
1 364 0 1028
1 366 0 822
1 368 0 864
1 372 0 557
1 376 0 535
1 384 0 419
1 408 0 268
1 432 0 214