Hong-Guang Analyses a= cross so many studies are notoriously difficult, especially with different = routes of administration. My personal experience is that the most com= mon cause for this sort of thing is errors in the data set. Make sure th= at the dose and concentration units are the same for all studies, as well a= s weight, height etc. If the populations are (relatively) the same ac= ross the studies, and the drug is the same (same formulation), and one stud= y isn't with ketoconazole (or other inhibitor/inducer), the error is almost= certainly in the data set. Again, in my experience, additional doses= are a frequent source of error. Also check that you are administerin= g the drug in the correct compartment. I assume that the dose for the= iv is going into compartment 2 for ADVAN4? All observtions are compa= rtment 2? (You'll need to specifiy the compartment the dose and observation= goes into for this model, since, I think you'll have doses going into comp= 1 and 2, extravascular and iv) I have a few plots that I like to ma= ke: -= Cumulative dose for each person vs time -Histogram of interdose intervals (this = will pick up a common one for me, where I give one too many additional dose= s - you'll have an interdose interval of 0, two doses given at the same tim= e). -= font>Histogram of interval between observation and most recent dose. Mark= Sale MD Next Level Solutions, LLC www.NextLevelSolns.com 919-846-9185 -------- Original Message -------- .....=
....... $SUBROUTINE ADVAN4 TRANS4 $=
PK ETAMX = 10 SI1=0=
SI2=0  = ; SI3=0 SI4=0 SI5=0 &n= bsp; SI6=0 IF (STDY .EQ. 1) SI1=
=1 ; iv IF (STDY .EQ. 2) SI2=1 &= nbsp; ; iv IF (STDY .EQ. 3) SI3=1 ; epi= dural IF (STDY .EQ. 4) SI4=1 ; iv &n= bsp; IF (STDY .EQ. 5) SI5=1 ; rectal &nb= sp; IF (STDY .EQ. 6) SI6=1 ; oral &nbs=
p; IV = SI1+SI2+SI4 ;intravascular dosing ;APPARENT=
CLEARANCE TVCL=popcl PPVCL= =bsvcl IF (ABS(PPVCL) .GE. ETAMX) EXIT 1 10 = CL=TVCL*EXP(PPVCL) ;CENTRAL VOLUME O= F DISTRIBUTION TVV2=popv2 PPV= V2=bsvv2 IF (ABS(PPVV2) .GE. ETAMX) EXIT 1 20 = V2=TVV2*EXP(PPVV2) ;INTERCOMPARTMENTAL CLE=
ARANCE TVQ=popq PPVQ=bsvq <= br> IF (ABS(PPVQ) .GE. ETAMX) EXIT 1 30 &n= bsp; Q=TVQ*EXP(PPVQ) ;PERIPHERAL VOLUME OF DISTRIBUTION &nb= sp; TVV3=popv3 PPVV3=bsvv3 = IF (ABS(PPVV3) .GE. ETAMX) EXIT 1 40 V3= =TVV3*EXP(PPVV3) ;FIRST ORDER ABSORPTION RATE CONSTANT &nbs= p; TVKA=SI3*ka3+SI5*ka5+SI6*ka6 PPVKA= =bsvka IF (ABS(PPVKA) .GE. ETAMX) EXIT 1 50<= br> KA=TVKA*EXP(PPVKA) ;LAG TIME &n= bsp; TVLAG=SI3*lag3+SI5*lag5+SI6*lag6 PPVLAG= =bsvlag IF (ABS(PPVLAG) .GE. ETAMX) EXIT 1 6= 0 ALAG1=TVLAG*EXP(PPVLAG) ;BIOAVAILABILI=
TY (BA) TVF1=SI3*f13+SI5*f15+SI6*f16  = ; PPVF1=bsvf1 IF (ABS(PPVF1) .GE. ETAMX) EXIT= 1 70 BA=TVF1*EXP(PPVF1) = IF (IV .GE. 1) THEN &n= bsp; F1=1 ELSE &n= bsp; F1=BA ENDIF ;ZERO ORDER ABS=
ORPTION DURATION TVD2=SI1*d21+SI2*d22+SI4*d24 &n= bsp; PPVD2=bsvd2 IF (ABS(PPVD2) .GE. ET= AMX) EXIT 1 80 D2=TVD2*EXP(PPVD2)  =
; RMIN=AMT/(60*D2) ;mcg/minute ; SCA= LING FOR CENTRAL COMPARTMENT (I.E., CONCENTRATION COMPARTMENT) &nb= sp; S2=V2 ; DOSE IN MCG, CONCENTRATION IN NG= /ML=MCG/L $ERROR = IPRED = F IF (MDV .EQ. 0) THEN &nb= sp; W = SQRT(add**2 + F*F*prop**2)  = ; ELSE W = 1  = ; ENDIF IRES=DV-IPRED &nbs=
p; IF (W .EQ. 0) THEN I= WRES=IRES ELSE &nb= sp; IWRES=IRES/W ENDIF &nbs=
p; Y=F+W*eps1*EXP(bsvres) $THETA (0,11.5) &nb=
sp; ;popcl = (0,24.1)  = ; ;popv2 &nb= sp; (0,12.9) ;p= opq = (0,8.22) ;popv3 &n= bsp; (0,0= .14) ;ka3 &n= bsp; (0,0.109) &= nbsp; ;ka5 = (0,0.397) ;ka6 &n= bsp; (0 FIX) &nb= sp; ;lag3 &n= bsp; (0 FIX) &nb= sp; ;lag5 &n= bsp; (0 FIX) &nb= sp; ;lag6 (0,4.93) = ;f13 (0,9.19) &nbs= p; ;f15 (0,0.523) &= nbsp; ;f16 (0,0.00072) ;d21  = ;(0,0.00007) ;d22 (0,0.00003) ;d24 = (0, 0.01) ;add &n= bsp; (0, 0.05) = ;prop $OMEGA 0.828 ;bsvcl $OMEGA 1.63 ;bsvv2$OMEGA 0 FIX ;bsvq $OMEGA 0 FIX ;bsvv3 $OMEGA 0 FIX ;bsvka $OME= GA 0 FIX ;bsvlag $OMEGA 0 FIX ;bsvf1 $OMEGA 0 FIX ;bsvd2 $OMEGA 0 = FIX ;bsvres $SIGMA 1. FIX ; eps1 $ESTIMATION=
NOABORT MAXEVAL=9999 POSTHOC PRINT=5 SIGDIGITS=3 MSFO= &n= bsp; METHOD=CONDITI= ONAL INTERACTION ;$COV PRINT=E $TABLE ID STDY TIME =
DV IPRED AMT MDV CMT CL V2 Q V3 KA ALAG1 F1 D2 RATE RMIN ETA1 ETA2 ETA3 ETA=
4 ETA5 ETA6 ETA7 ETA8 ETA9 IWRES IR= ES WT BWT AGEY AGED GAGE NOPRINT O= NEHEADER FILE= ================
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