Dear all, I'm now developing a simple PBPK structural model in NONMEM. The input 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 the 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$MODELCOMP = (LIV) ; 1 - LIVER COMPARTMENTCOMP = (KID) ; 2 - KIDNEY COMPARTMENTCOMP = (MUS) ; 3 - MUSCLE COMPARTMENTCOMP = (INJ) ; 4 - INJECTIONSITE COMPARTMENT RECEIVING DOSECOMP = (VEN) ; 5 - VENOUS COMPARTMENTCOMP = (OUT) ; 6 - KIDNEY EXCRETION COMPARTMENT$PK; ------------------------ TWO ABSORBTION PHASE-------------------- ;PHSF = 0.714 ; FAST PHASE ABSORPTION FRACTIONPHSS = 0.286 ; SLOW PHASE ABSORPTION FRACTIONKF = 0.032334 ; FAST PHASE ABSORPTION 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*0.1398*(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 ;KG;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))$DES;--------------------COMPARTMENT CONCENTRATIONS-------------------;C1 = A(1)/VLIVC2 = A(2)/VKIDC3 = A(3)/VMUSC4 = A(4)/VINJC5 = A(5)/VVENDADT(1)=QLIV*(C5-C1/PLIV)DADT(2)=(QKID*(C5-C2/PKID)-C2*EXCR)DADT(3)=QMUS*(C5-C3/PMUS)DADT(4)=(QINJ*(C5-C4/PMUS))DADT(5)=(QLIV*C1/PLIV+QKID*C2/PKID+QMUS*C3/PMUS+QINJ*C4/PMUS-QVEN*C5)DADT(6)=EXCR$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
