Re:

1) Likely your data units are off by a few orders of magnitude. (maybe concentrations are shown in ng/mL or maybe in ug/mL or pg/mL) 2) perhaps your bioavailability is also small 3) perhaps your drug units are in ug instead of mg? 4) Try scaling S2=V/1000000 to compensate 5)Don't put upperbounds on your volume till you know the right scale and order of magnitude Good luck! - Joseph Joseph Kahn, Ph.D. Novartis Pharmaceuticals Corporation Novartis Pharmaceuticals Corporation One Health Plaza East Hanover, NJ 07936-1080 USA Phone: +1 862 7783939 Email : [email protected] Susan Al taher <[email protected]> Sent by: [email protected] 03/05/2011 12:34 PM To <[email protected]> cc Subject Hi I am trying to build a structural model for an oral drug. I am getting extremely large and unreasonable values for vd, eg a billion L, putting an upper limit on theta will give a near boundary warning. Does anyone have an idea why this might occur and how to solve it. This is part of the input file: $SUBROUTINE ADVAN2 TRANS2 $PK TVCL = THETA(1) CL = TVCL*EXP(ETA(1)) V = THETA(2) KA = THETA(3) S2 = V $THETA (0,10) $THETA (0,20) $THETA 2 FIXED Best regards Susan