Re: time-dependent clearance model

On 3/4/12 8:51 PM, "Wang, Xiaofeng" <[email protected]> wrote: > Hi Katya, > > Thank you. I double checked the units. mcg for AMT, ng/mL for DV, and L for > CL. I think there is no problem with the units. Since I am using > log-transformed data, does that influence the units? > > I will try kicking in CLSS after day 1. For 6 observations per patients, what > is the reasonable number of ETAs? > > Best, > Xiaofeng > > From: [email protected] [[email protected]] on behalf of > Ekaterina Gibiansky [[email protected]] > Sent: Sunday, March 04, 2012 8:53 PM > To: '[email protected]' > Subject: Re: [NMusers] time-dependent clearance model > > Xiaofeng, > > Such a large difference suggests you may have a problem with units: check AMT, > DV, and the parameter S2 for consistency. > A couple of other points: > - If the full induction is expected by day 7, and you only have data on day 1 > and after day 7, you may not be able to estimate KIN. You may be better off > with the model where there is CLI on day 1 and CLSS on days >1 (And you will > not need $DES for that model). > - You have 6 observations per subject and you have 7 ETAs, it is too many, > your model should be overparameterized (Check whether relative standard errors > are large). > > Regards, > Katya > Ekaterina Gibiansky, Ph.D. > CEO&CSO, QuantPharm LLC > Web: www.quantpharm.com http://www.quantpharm.com > Email: EGibiansky at quantpharm.com > > > On 3/4/2012 5:33 PM, Wang, Xiaofeng wrote: >> 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 >> >> >> >> >> >> >> >> >> >> >> >> >> >