ADVAN3 TRANS3 Problem

From: Rebecca Wrishko <wrishko@unixg.ubc.ca> Subject: ADVAN3 TRANS3 Problem Date: Wed, 03 Nov 1999 13:46:58 -0800 Fellow NONMEM Users, I am a member of a research group that is just commencing utilization of NONMEM for Population and Bayesian analyses. We are novices with both NONMEM and Digital Visual Fortran, but were able to install NONMEM V (1.1) under the MS-DOS prompt launched under F-90 of DF. Further, the installation was tested using the routine outlined in Appendix 5 (cd run nmfe5 etc.). Also, I successfully duplicated the control3 and data3 in microsoft and excel, saved under the .txt and .prn extensions respectively, and generated the same report as that provided in report3 of the sample files. We are attempting to model vancomycin and gentamicin pharmacokinetics in general pediatric and neonatal patients. Utilizing data from one subject that had been previously modeled with WinNonlin, I created the control stream and data files for both one-compartment (ADVAN1 TRANS2) two compartment (ADVAN3 TRANS3) analyses. Providing the reparameterization line of K=CL/V was included in the $PK block, NONMEM generated estimates of the CL and V I requested. However, I have experienced much difficulty in generating estimates of CL, V, VSS using the ADVAN3 TRANS3 routine. The most common error message I receive is that V is larger than VSS. Should I first implement the TRANS1 routine to generate estimates of K, K21, and K12, in order that these may then be incorporated into the $pk block to provide the variables for the reparameterization lines (K=CL/V; K12=Q/V; K21=Q/(VSS-V))? The following represents a sample of a $PK and $THETA code that generated the above mentioned error message, I did not include OMEGA and SIGMA codes because the data reflects concentration measurements from one individual. Any suggestions you may have to solve this frustrating dilemma would be greatly appreciated. $PK CL=THETA(1) V=THETA(2) VSS=THETA(3) Q=THETA(4) K=CL/V K12=Q/V K21=Q/(VSS-V) $THETA (0,,4) (0,,7) (0,,10) (0,,4)