From: "Ralph Quadflieg" <quadflieg@uni-bonn.de>

Date: 28 Sep 1998 14:16:27 -0400

I am a new NONMEM user and I have some difficulties in writing a control file for my pk problem:

I would like to model 3 data sets (3 different settings) with a 4 compartment model (depot, central, peripher1, peripher2).

a) the depot comp. should be the dosing compartment with a first order process to the central comp. (is not known) a bioavailability factor (is not known, oral appl.) and a lagtime parameter (is not known)

b) the central comp. should be the dosing comp. with two different constant rates (are known) and a bioavailability factor = 1 (iv infusion)

I thought that this should be a problem for ADVAN6 and TRANS1 with a MODEL record like this:

ALAG1 = THETA(9) * EXP(ETA(9))

and a corresponding data file with RATE CMT EVID PCMT data items.

But there are problems due to the MODEL block, which I cannot solve (especially the LINK statement).

I am a bit confused about the different possibilities of working with the LINK statements within the MODEL block or within th PK block, I should say.

The MODEL is established with differential equations, but with this control file the run takes a lot of time. (around one hour).

I would be pleased if there was somebody who can help me.

http://www.pharma.uni-bonn.de/pharmtech/

From: alison@c255.ucsf.EDU (ABoeckmann)

Date: 28 Sep 1998 16:13:20 -0400

Ralph Quadflieg asked about a 4 compartment model.

The error messages arise because LINK clauses in $MODEL are used only with a user-written PK routine *and* with either ADVAN5 or ADVAN7.

With $PK, he should omit the LINK clauses.

1) With ADVAN6 8 or 9, use a $DES block to define the differential equations, using the K's defined in $PK.

2) Since the kinetics are linear, ADVAN5 or ADVAN7 can be used. NMTRAN will understand that these statments in $PK imply the links between compartments, providing that the lower case k's are changed to upper case K's:

Note that the following are also needed:

With NONMEM V, the analytic solution to the 4 compartment problem has been supplied as ADVAN12. This will give faster run times than the general ADVAN routines 5,6,7,8,9.

Omit the $MODEL block. Use the original $PK block (with uppercase k's as noted above).

With ADVAN12 TRANS1, the statement

It is also possible to use ADVAN12 with TRANS4. This is a very similar parameterization, with slightly different notation.

See Users Guide VIII, ADVAN12 and TRANS4 entries (or nmhelp advan12, nmhelp trans4), for the details.