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RE: PBPK structural model in NONMEM!

From: ke fang <fang.coco>
Date: Tue, 29 Dec 2009 13:59:24 +0800 (CST)

Dear Masoud and Guzy,   Thanks for your comments, and sorry for my =
late reply.    I recode my control stream file and data file, but i=
'm not quite sure if it is appropriate. Please correct me if i was wrong! T=
hanks in advance!   Here is the control stream. $PROB WBPBPK POPUL=
ATION MODEL $INPUT ID TIME CONC=DV AMT WT EVID CMT MDV $DATA ..\PBPK.=
TXT IGNORE=# $SUBROUTINES ADVAN8 TOL=3 $MODEL COMP = (LIV,NODOS=
E) ; 1 - LIVER COMPARTMENT COMP = (KID,DEFOBS,NODOSE) ; 2 - KIDNEY COMP=
ARTMENT COMP = (MUS,NODOSE) ; 3 - MUSCLE COMPARTMENT COMP = (INJ,NO=
DOSE) ; 4 - INJECTIONSITE COMPARTMENT RECEIVING DOSE COMP = (VEN,NODOSE=
) ; 5 - VENOUS COMPARTMENT COMP = (OUT,NODOSE) ; 6 - KIDNEY EXCRETION C=
OMPARTMENT COMP = (PHSF) ; 7 - FAST PHASE COMP = (PHSS) ; 8 - SLOW =
PHASE COMP = (OTH,NODOSE) ; 9 - OTHER TISSUE $PK "FIRST " COMMON =
/PRCOMG/ IDUM1,IDUM2,IMAX " INTEGER IDUM1,IDUM2,IMAX " IMAX=100000 =
; ------------------------ TWO ABSORBTION PHASE-------------------- ; KF =
= 0.32334 ; FAST PHASE ABSORPTION RATE KS = 0.0835 ; SLOW PHASE ABSOR=
PTION RATE ; ------------------------- BLOOD FLOWS (Q,L/HR) -------------=
------- ; QVEN = 0.25*WT**0.75 ;L/H/KG; QLIV =QVEN*0.3053;L/H/KG;=

EN*0.2524*(0.5/WT) ;L/H/KG; QOTH=QVEN-QLIV-QKID-QMUS-QINJ ;----------=
------------------TISSUE VOLUMES (V,L)----------------------; VLIV =0.0=
294*WT ;KG; VKID =0.004*WT ;KG; VMUS =0.4007*WT ;KG; VINJ =0.5 =
;KG; VVEN =0.06*WT ;KG; VOTH=WT-VLIV-VKID-VMUS-VINJ-VVEN ;-------=
---------------------PARTITION COEFFICIENTS-------------------; PLIV = =
1.94 PKID = 2.38 PMUS = 1.11 POTH = 0.05 ;-------------------=
--KIDNEY EXCRETION-------------------; EXCR=(THETA(1))*EXP(ETA(1)) ;P=
LIV=THETA(2)*EXP(ETA(2)) ;PKID=THETA(3)*EXP(ETA(3)) ;PMUS=THETA(4=
)*EXP(ETA(4)) ;POTH=THETA(5)*EXP(ETA(5)) $DES ;--------------------=
COMPARTMENT CONCENTRATIONS-------------------; C1 = A(1)/VLIV ; CONCENT=
RATION IN LIVER C2 = A(2)/VKID ; CONCENTRATION IN KIDNEY C3 = A(3)/=
VMUS ; CONCENTRATION IN MUSCLE C4 = A(4)/VINJ ; CONCENTRATION IN INJECT=
ION SITE C5 = A(5)/VVEN ; CONCENTRATION IN VENOUS C9 = A(9)/VOTH ; =
CONCENTRATION IN OTHER TISSUE DADT(1)=QLIV*(C5-C1/PLIV) DADT(2)=(QK=
ID*(C5-C2/PKID)-A(2)*EXCR) DADT(3)=QMUS*(C5-C3/PMUS) DADT(4)=(KF*A(=
7)+KS*A(8)+QINJ*(C5-C4/PMUS)) DADT(5)=(QLIV*C1/PLIV+QKID*C2/PKID+QMUS*C=
3/PMUS+QINJ*C4/PMUS-QVEN*C5) DADT(6)=EXCR*A(2) DADT(7)=-KF*A(7) D=
ADT(8)=-KS*A(8) DADT(9)=QOTH*(C5-C9/POTH) $ERROR Y=A(2)/VKID+EP=
S(1) ;------------------------INITIAL ESTIMATES--------------------------=
----; $THETA(0.01,7.12)        ; 1-EXCR ;$THETA(1,5.01)    =
      ; 2-PLIV ;$THETA(1,3.77)          ; 3-PKID ;$THET=
A(0.2,0.758)          ; 4-PMUS ;$THETA(0,0.0889)       =
   ; 5-POTH $OMEGA(0.09)      ; 1-EXCR ;$OMEGA(0.09) ;$OMEGA(=
0.09) ;$OMEGA(0.09) ;$OMEGA(0.09) ;$OMEGA(0.09) $SIGMA(1)    =
   ; 1-ERROR $EST PRINT=5 MAX=9990 POSTHOC SIGDIG=7 METHOD==
0 $COV MATRIX=R $TABLE ID TIME CONC WT AMT NOPRINT ONEHEADER FILE=P=
BPK.FIT Here is part of data file. #ID TIME CONC AMT WT EVID CMT =
MDV 1 0 0 492.66 22.3 1 7 1 1 0 0 197.34 22.3 1 8 1 1 24 52.462 0 22.=
3 0 2 0 2 0 0 492.66 22.4 1 7 1 2 0 0 197.34 22.4 1 8 1 2 72 7.704 0 =
22.4 0 2 0 Ke, Fang
Received on Tue Dec 29 2009 - 00:59:24 EST

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