Dear nmusers, I have a drug with clearance autoinduction. I have sparse data(three observations on day 1, two between day 7 and 14, and one on day 28). I am trying to run a time-dependent clearance model. I tried FO and FOCEI, but I always got unreasonable estimate for the initial clearance (CLI) which is about 0.15 L/h (from knowledge of previous studies, the reasonable initial clearance should be around 20 L/h and maximum induction occurs around day 7). Could someone give me some advice about my model and my data? Thank you.
Xiaofeng The CTL file: $PROB $INPUT C ID TIME AMT DV MDV EVID ADDL II CMT $DATA C:/ IGNORE=C $SUBROUTINES ADVAN6 TOL=6 $MODEL NCOMPARTMENTS=3 COMP=(DEPOT,DEFDOSE) COMP=(CENTRAL,DEFOBS) COMP=(PERIP) $PK CLI=THETA(1)*EXP(ETA(1)) CLSS=THETA(2)*EXP(ETA(2)) KIN=THETA(3)*EXP(ETA(3)) V2= THETA(4)*EXP(ETA(4)) Q= THETA(5)*EXP(ETA(5)) V3= THETA(6)*EXP(ETA(6)) KA= THETA(7)*EXP(ETA(7)) S2=V2 K23=Q/V2 K32=Q/V3 $DES CL=CLSS-(CLSS-CLI)*EXP(-KIN*T) K20=CL/V2 DADT(1)=-KA*A(1) DADT(2)=KA*A(1)+K32*A(3)-K23*A(2)-K20*A(2) DADT(3)=K23*A(2)-K32*A(3) $ERROR IPRE=LOG(1) IF(F.GT.0) IPRE=LOG(F) Y = IPRE+EPS(1) $EST METHOD=0 POSTHOC PRINT=10 MAX=9999 SIG=2 NOABORT MSFO=050.MSF $THETA (0, 20);[CLI] (0, 65);[CLSS] (0, 0.02) ;[KIN] (0, 45);[V2] (0, 5);[Q] (0, 58);[V3] (0, 0.2);[KA] $OMEGA .25 .25 .25 .25 .25 .25 .25 $SIGMA .2 $COV PRINT=E $TABLE ID TIME DV CLI CLSS KIN V2 Q V3 KA IPRE CWRES ONEHEADER NOPRINT FILE=050.TAB $TABLE ID TIME CLI CLSS KIN V2 Q V3 KA FIRSTONLY NOAPPEND NOPRINT FILE=050.PAR $TABLE ID ETA1 ETA2 ETA3 ETA4 ETA5 ETA6 ETA7 FIRSTONLY NOAPPEND NOPRINT FILE=050.ETA $TABLE ID TIME CLI CLSS KIN V2 Q V3 KA FIRSTONLY NOAPPEND NOPRINT FILE=PATAB050
