1)

All files are distributed on a single CD.

2)

Some files are present on the CD that were not present on the diskettes. These are: readme_6.1.0.txt and readme_6.1.0.doc, MS-DOS batch files nmg77.bat, nmg95.bat and nmfe6wfl386.bat, FORTRAN programs SEPG77, MAKEG77BAT and MAKEG95BAT. Unix versions of all files can be found in a single file nonmemvi.tar. In addition to on-line help files for use at the command line, the CD includes on-line help as HTML files (Hyper-NMHelp) and NONMEM Users Guides in pdf format.

3)

There is no single-precision version of NONMEM VI. References to the single-precision version in this guide should be ignored.

4)

You must replace all of NONMEM, PREDPP, and NM-TRAN. Do not mix new and old versions of the various components of the NONMEM system! It is best to install the new versions separately from NONMEM V.

5)

The MS-DOS installation utility is now called CDSETUP6.BAT. The UNIX installation utility is still called SETUP. UNIX shell scripts NMFE6 and MS-DOS batch file NMFE6.BAT are used to run NONMEM VI.

6)

There is now a single INCLUDE file named SIZES. This file contains all the constants previously contained in NSIZES, PSIZES, TSIZES and LSIZES. SIZES contains a new variable, MAXIDS, the maximum number of individuals in a data set. The default value is 1000. The SIZES file is present only in the main NONMEM directory (e.g., nmvi), not in the directories for the components (e.g., nm, tr, etc.).

7)

NONMEM, PREDPP and NM-TRAN consist of more routines than previously. Some old routines no longer exist, and some new routines have been added.

8)

More disk space and RAM is needed for NONMEM VI vs. NONMEM V. However, all modern computers can run NONMEM VI easily.

9)

When re-running old NONMEM problems, please be aware of the following facts:

• NONMEM output has changed somewhat. In particular, there are changes to the first pages of output, in which NONMEM (and PREDPP) describe their inputs.
• It is possible that the results of the Estimation and Covariance Steps may be different than with earlier versions of NONMEM.
• Old Model Specification files (MSF’s) and old NM-TRAN Library Control files (FLIB) cannot be re-used with the new release.
• Old Fortran subroutines (e.g., PRED, MODEL, PK, DES, AES routines) (whether user-coded or generated by NM-TRAN) cannot be re-used without certain modifications.
• Old NM-TRAN control streams and NM-TRAN data files can be re-used.
• Old NONMEM data files can be re-used.
• In general, we have tried to make the new release upwards compatible from the old release. However, there are a few exceptions. Changes to NM-TRAN, NONMEM and PREDPP are described in more detail in the Introduction to Version VI. They may affect the outcome of certain runs.