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RE: advan8 vs. advan13

From: Ludden, Thomas <Thomas.Ludden>
Date: Mon, 2 Nov 2009 08:54:51 -0500

I agree with Nick's assessment. TRAN1 on the $SUBROUTINE statement
should not make a difference with ADVAN8. Can you provide us the
control stream and at least a part of the data file so that we can
explore this in more detail.


From: owner-nmusers
On Behalf Of Nick Holford
Sent: Sunday, November 01, 2009 1:57 PM
To: nmusers
Subject: Re: [NMusers] advan8 vs. advan13


The TRANSn option is only meaningful for those ADVANs (i.e. 1-4,11,12)
which implement a closed form solution of the PK model. TRANS1 does
nothing except keep the linker happy. Because it is the default it need
never be explicitly specified for ADVAN5-9,13.

"TRANS1 Dummy, or null, translator; may be used with all ADVAN
routines. It is the default." NONMEM7 Help

Adding it to those ADVANs which solve ODEs or use matrix exponential
solutions should make no difference to anything. If you find that adding
TRANS1 changes the behaviour of ADVAN8 then this is a bug.


> Hello Nonmem Users,
> When I tried simple simulations and changed advan13 to advan8, some
concentrations changed. Equations were stiff. Then I added TRANS1 to
the $SUBROUTINE statements. ADVAN13 output did not change. ADVAN8
output changed and looked exactly like ADVAN13 output. Do you know what
> (Another thing I noted is that when IMP is used, the lower boundary
for bioavailability cannot be 0.)
> Thanks,
> Pavel
> ----- Original Message -----
> From: nonmem
> Date: Sunday, November 1, 2009 8:34 am
> Subject: Re: [NMusers] advan8 vs. advan13
> To: nmusers
> > It seems like advan8 has integration difficulties when both LAG
> > time and variability in Ka are implemented. Method=IMP has
> > dificulties when advan8 has integration difficulties. Instead
> > if reporting issues, it keeps running. The objective function
> > is very low even when bioavailability is almost zero. Removing
> > LAG and eta of Ka may fix it.
> >
> > ----- Original Message -----
> > From: nonmem
> > Date: Sunday, November 1, 2009 12:04 am
> > Subject: [NMusers] advan8 vs. advan13
> > To: nmusers
> >
> > > Hello NONMEM users,
> > >
> > > Because advan13 was recomended for both stiff and nonstiff
> > > differential equations, I used it for stiff differential
> > > equations. It appeared that some results looked too sensitive
> > > to a parameters representing a "slow" processes. I did not
> > > observe it with nonmem6. When I used advan8, the objective
> > > function changed from 10228.853 (the final value; diagnostic
> > > plots looked good) to 5512.594 (the first value; I im still
> > > waiting for the final value of the objective function).
> > >
> > > Does it mean that advan13 should be used with caution when the
> > > equations are stiff or advan13 cannot replace advan8?
> > >
> > > Thanks,
> > > Pavel
> > >
> >

Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
mobile: +64 21 46 23 53

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Received on Mon Nov 02 2009 - 08:54:51 EST

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