With Yoshi’s suggestion, you may try FORM as a covariate (e.g. if formulation is R, FORM=0 and T, FORM=1) and put it in the code as following
But I doubt all of theta 4,5,6,7 are necessary at this situation. If you want to consider any change in PK parameters by periods, use of IOV in the ETA terms may be better answer. Good Luck Dong-Seok Yim $PK KA=(THETA(1) + FORM*THETA(4))*EXP(ETA(1)) CL=(THETA(2)+ FORM*THETA(5))*EXP(ETA(2)) V=(THETA(3) + FORM*THETA(6))*EXP(ETA(3)) F1=1 + FORM*THETA(7) From: [email protected] [mailto:[email protected]] On Behalf Of [email protected] Sent: Wednesday, March 16, 2011 3:19 PM To: [email protected]; [email protected] Subject: RE: [NMusers] NONMEM codes about PK analysis from a cross-over study design Dear Xipei I recommend you use EVID=4 at time=0 in the 2nd period on the dataset. Also you consider the relative BA(F1 parameter). ID TIME AMT DV EVID DRUG 1 0 100 . 1 1 1 0.3 . 0.7 0 1 1 0.5 . 2 0 1 .... 1 48 . 0.6 0 1 1 0 100 . 4 2 1 0.3 . 0.3 0 2 1 0.5 . 1.6 0 2 $PK KA=THETA(1)*EXP(ETA(1)) CL=THETA(2)*EXP(ETA(2)) V=THETA(3)*EXP(ETA(3)) F1=1 IF (DRUG.EQ.2) THEN KA=THETA(4)*EXP(ETA(4)) CL=THETA(5)*EXP(ETA(5)) V=THETA(6)*EXP(ETA(6)) F1=THETA(7) *EXP(ETA(7)); Relative BA parameter ENDIF Thanks! Yoshi From: [email protected] [mailto:[email protected]] On Behalf Of wangxipei Sent: Wednesday, March 16, 2011 2:51 PM To: nmusers Subject: [NMusers] NONMEM codes about PK analysis from a cross-over study design Dear NONMEM users, I have a data set from a bioavailablity study (2×2 study design). 18 people took a single dose of a marketed drug (marked as R), then after a wash-out period, took a single dose the corresponding generic drug (marked T). I want to estimate the PK parameters of T and R seperately. One approach we handle the dataset is to consider the 18 people as 36 people. Is it right? I still want to handle them as 18 people. I read something useful in the NONMEM guides on EVID, but still comfused about the data file structure and the NONMEM codes. Thank you very much ahead for any comments. Xipei Wang Beijing, China Part of my codes and data are as below: data set: ID TIME AMT DV EVID DRUG 1 0 100 . 1 1 1 0.3 . 0.7 0 1 1 0.5 . 2 0 1 .... 1 48 . 0.6 0 1 1 0 . . 3 . 1 0 100 . 1 2 1 0.3 . 0.3 0 2 1 0.5 . 1.6 0 2 .... NONMEM CODES： $INPUT ID TIME AMT DV EVID DRUG $DATA sample.csv $SUBROUTINES ADVAN2 TRANS2 $PK KA=THETA(1)*EXP(ETA(1)) CL=THETA(2)*EXP(ETA(2)) V=THETA(3)*EXP(ETA(3)) IF (DRUG.EQ.2) THEN KA=THETA(4)*EXP(ETA(4)) CL=THETA(5)*EXP(ETA(5)) V=THETA(6)*EXP(ETA(6)) ENDIF S2=V/1000 $ERROR Y=F+ERR(1) $THETA (0, 2) ;KA (0, 8) ;CL (0, 4) ;V (0, 2) ; (0, 8) ; (0, 4) ; $OMEGA 0.04 0.04 0.04 0.04 0.04 0.04 $SIGMA 0.04 $ESTIMATION MAXEVAL=9999 METHOD=1
