From: Mouksassi Mohamad-Samer <*mohamad-samer.mouksassi*>

Date: Thu, 6 Aug 2009 02:23:12 -0400

Hello Sherwin,

All SS routines source code are located at the C:\nmvi\pr folder.

Each Advan closed form model has specific routines (and equations for =

SS) that can be used with it.

For linear models the magic factor for steady state computation will be: =

exp(-rate.constant.time)/(1-exp(-rate.constant.Tau).

Monolix guide: Monolix31_PKPD_library.pdf has a lot of SS equations for =

commonly used models.

Of course general Advans have their general SS routines too and as Nick =

mentioned there is some root finding going on:

a comment from the SS6.FOR routine reads

C SS IS SOLUTION A OF: 0=DADT(A)+R

C APPROXIMATION: DADT(A)=DADT(0)+DA*A

C 0=DADT(0)+DA*A+R

C A=-DAINV*(DADT(0)+R)

...

Happy Reading !

Bests,

Samer

-----Original Message-----

From: owner-nmusers

Sent: Wed 8/5/2009 15:44

To: nmusers

Subject: Re: [NMusers] Steady state model

Sherwin,

I dont understand exactly how NONMEM computes the steady state value but =

with ODEs it seems to be done using a numerical root finding procedure

i.e. solves for the amt in each of the compartments when all the DEs

have a value of zero.

The amt in each compartment is set to the steady state value. There is

no initial 'parameter' for the compartment. Compartment amounts are

variables. Parameters are constants. Parameters (e.g. THETA values) are

used in the ODEs to define the DE values.

Perhaps Alison Boechmann (who wrote the code) could give a more thorough =

answer?

Nick

Sherwin K Sy wrote:

*> Dear NONMEM users,
*

*>
*

*> I'm wondering what equation or ODE is used in NONMEM when the steady
*

*> state is set (i.e. SS = 1). Is it the case that the initial =
*

parameter

*> for the compartment is set to a different value? If so, how does
*

*> NONMEM set this value?
*

*>
*

*> I would appreciate if anyone can provide me with a reference or point
*

*> me to where I can find this information, including the type of
*

*> equation used for extravascular, iv bolus and iv infusion models.
*

*>
*

*> Thanks,
*

*>
*

*> Sherwin
*

*>
*

*>
*

--

Nick Holford, Professor Clinical Pharmacology

Dept Pharmacology & Clinical Pharmacology

University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New =

Zealand

n.holford

mobile: +64 21 46 23 53

http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Thu Aug 06 2009 - 02:23:12 EDT

Date: Thu, 6 Aug 2009 02:23:12 -0400

Hello Sherwin,

All SS routines source code are located at the C:\nmvi\pr folder.

Each Advan closed form model has specific routines (and equations for =

SS) that can be used with it.

For linear models the magic factor for steady state computation will be: =

exp(-rate.constant.time)/(1-exp(-rate.constant.Tau).

Monolix guide: Monolix31_PKPD_library.pdf has a lot of SS equations for =

commonly used models.

Of course general Advans have their general SS routines too and as Nick =

mentioned there is some root finding going on:

a comment from the SS6.FOR routine reads

C SS IS SOLUTION A OF: 0=DADT(A)+R

C APPROXIMATION: DADT(A)=DADT(0)+DA*A

C 0=DADT(0)+DA*A+R

C A=-DAINV*(DADT(0)+R)

...

Happy Reading !

Bests,

Samer

-----Original Message-----

From: owner-nmusers

Sent: Wed 8/5/2009 15:44

To: nmusers

Subject: Re: [NMusers] Steady state model

Sherwin,

I dont understand exactly how NONMEM computes the steady state value but =

with ODEs it seems to be done using a numerical root finding procedure

i.e. solves for the amt in each of the compartments when all the DEs

have a value of zero.

The amt in each compartment is set to the steady state value. There is

no initial 'parameter' for the compartment. Compartment amounts are

variables. Parameters are constants. Parameters (e.g. THETA values) are

used in the ODEs to define the DE values.

Perhaps Alison Boechmann (who wrote the code) could give a more thorough =

answer?

Nick

Sherwin K Sy wrote:

parameter

--

Nick Holford, Professor Clinical Pharmacology

Dept Pharmacology & Clinical Pharmacology

University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New =

Zealand

n.holford

mobile: +64 21 46 23 53

http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Thu Aug 06 2009 - 02:23:12 EDT