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PBPK structural model in NONMEM!

From: ke fang <fang.coco>
Date: Sun, 13 Dec 2009 14:27:40 +0800 (CST)

Dear all,
  I'm now developing a simple PBPK structural model in NONMEM. The inpu=
t to the PBPK model was a i.m. injection, and the only output was the renal=
 excretion. Because the drug was a long acting formulation, so  I try to =
model the absorption into a fast phase and a slow phase. Now, here comes th=
e problem. I don't know how to get DOSE into the model. Here is the control=
 stream file:
$PROB WBPBPK POPULATION MODEL$INPUT ID TIME CONC=DV AMT WT EVID CMT$DATA =
...\PBPK.TXT IGNORE=#$SUBROUTINES ADVAN6 TOL=3$MODELCOMP = (LIV) ; 1 -=
 LIVER COMPARTMENTCOMP = (KID) ; 2 - KIDNEY COMPARTMENTCOMP = (MUS) ; 3=
 - MUSCLE COMPARTMENTCOMP = (INJ) ; 4 - INJECTIONSITE COMPARTMENT RECEIVI=
NG DOSECOMP = (VEN) ; 5 - VENOUS COMPARTMENTCOMP = (OUT) ; 6 - KIDNEY E=
XCRETION COMPARTMENT$PK; ------------------------ TWO ABSORBTION PHASE-----=
--------------- ;PHSF = 0.714 ; FAST PHASE ABSORPTION  FRACTIONPHSS ==
 0.286 ; SLOW PHASE ABSORPTION FRACTIONKF = 0.032334 ; FAST PHASE ABSORPT=
ION ABSORPTION RATEKS = 0.00835 ; SLOW PHASE ABSORPTION ABSORPTION RATE; =
------------------------- BLOOD FLOWS (Q,L/HR) -------------------- ;QVEN =
= 2.049*WT ;L/H/KG;QLIV =QVEN*0.3053*(WT/25) ;L/H/KG;QKID =QVEN*0.139=
8*(WT/25) ;L/H/KG;QMUS =QVEN*0.2524*(WT/25) ;L/H/KG;QINJ = QVEN*0.2524*=
(0.5/WT/25) ;L/H/KG;;----------------------------TISSUE VOLUMES (V,L)------=
----------------;VLIV
 =0.0294*WT ;KG;VKID =0.004*WT ;KG;VMUS =0.4007*WT ;KG;VINJ =0.5 ;K=
G;VVEN =0.06*WT ;KG;;----------------------------PARTITION COEFFICIENTS--=
-----------------;PLIV = EXP(THETA(2))PKID = EXP(THETA(3))PMUS = EXP(=
THETA(4));---------------------KIDNEY EXCRETION-------------------;TVEXCR=
=EXP(THETA(1))EXCR=TVEXCR*EXP(ETA(1))$DES;--------------------COMPARTME=
NT CONCENTRATIONS-------------------;C1 = A(1)/VLIVC2 = A(2)/VKIDC3 ==
 A(3)/VMUSC4 = A(4)/VINJC5 = A(5)/VVENDADT(1)=QLIV*(C5-C1/PLIV)DADT(2=
)=(QKID*(C5-C2/PKID)-C2*EXCR)DADT(3)=QMUS*(C5-C3/PMUS)DADT(4)=(QINJ*(=
C5-C4/PMUS))DADT(5)=(QLIV*C1/PLIV+QKID*C2/PKID+QMUS*C3/PMUS+QINJ*C4/PMUS-=
QVEN*C5)DADT(6)=EXCR$ERRORY=A(3)/VMUS+EPS(1);--------------------------=
----INITIAL ESTIMATES--------------------------------;$THETA(0,0.5)    =
    ; 1-EXCR$THETA(0,1.82,10)        ; 2-PLIV$THETA(0,6.46,10) =
       ; 3-PKID$THETA(0,0.486)        ; 4-PMUS$OMEGA(0.5) =
     ; 1-EXCR$SIGMA(1)       ; 1-ERROR$EST PRINT=5
 MAX=9990 POSTHOC SIGDIG=3 METHOD=1$COV MATRIX=R$TABLE ID TIME CONC=
 WT AMT NOPRINT ONEHEADER FILE=PBPK.FIT
Can anyone give some hint?Thanks in advance!
Ke, Fang
Received on Sun Dec 13 2009 - 01:27:40 EST

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