Re: [NMusers] A problem with numerical integration difficulties for a complex model

From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
Date: Thu, 5 Jan 2017 11:32:49 -0500

I think it would help if you provide the code and the reference and the
sample data set: some published papers contain typos, so it is hard to
give a general advice based on limited information
Thanks
Leonid


On 1/5/2017 10:44 AM, Zhu, Penny wrote:
> Dear Ankekatrin, Jeroen and Sam
>
> Many thanks for your kind suggestions.
>
>
>
> I tried ADVAN9, ADVAN13 with different TOL numbers. They both returned
> errors as well.
>
>
>
> For ADVAN13
>
> ERROR IN LSODI1: CODE 205
>
> ERROR IN LSODI1: CODE 205
>
>
>
>
>
> For ADVAN9
>
> ERROR IN LSODA -1
>
> ERROR IN LSODA -5
>
>
>
> I also tried adding more simulation timepoints. I don’t think it made a
> difference.
>
>
>
> Does anybody have other suggestion? Should I try Monolix given that
> NONMEM has numerical difficulties
>
>
>
> Thank you very much and best regards!
>
> * *
>
> *Penny (Peijuan) Zhu, Ph.D.*
>
> Associate Director Clinical Pharmacology
>
>
>
> Cell: 862-926-9079
>
>
>
> PD Bio-Pharma CDMA
>
> Sandoz
>
> 1N025, 100 College Road West
>
> Princeton, NJ 08540
>
>
>
>
>
>
>
> *From:*ankekatrin.volz_at_uni-saarland.de
> [mailto:ankekatrin.volz_at_uni-saarland.de]
> *Sent:* Wednesday, January 04, 2017 3:33 PM
> *To:* Zhu, Penny <penny.zhu_at_sandoz.com>
> *Subject:* Re: [NMusers] A problem with numerical integration
> difficulties for a complex model
>
>
>
> Hey Penny,
> From my little experience with the TMDD modeling ADVAN 13 or 9 works
> better.
> Good luck
> Katrin
>
> Von: Sam Liao
> Gesendet: Mittwoch, 4. Januar 21:28
> Betreff: Re: [NMusers] A problem with numerical integration difficulties
> for a complex model
> An: Zhu, Penny, nmusers_at_globomaxnm.com <mailto:nmusers_at_globomaxnm.com>
>
> Hi Penny,
> You could try other ODE solver, such as ADVAN13 to see if you can get
> around this problem.
> But, If the data are too sparse, the time gap between two data points
> might be too long to solve the ODE, you may want to consider adding some
> dummy data points with EVID=2. Good luck with your TMDD modeling.
>
> Best regards,
> Sam Liao, PhD.
> Pharmax Research
>
> On 1/4/2017 8:53 AM, Zhu, Penny wrote:
>
>
>
> Dear all
>
> Sorry to bother you.
>
>
>
> I have encountered a problem with a complex model, involve a full TMDD
> PK model lined to a complicated multi-compartment PD model. I was only
> doing a simulation based on a published paper so I would prefer not to
> alter or simplify the model.
>
>
>
> The model kept having numerical difficulties no matter how I modify the
> TOL value (I have changed it from 0 to 6). And I am using ADVAN 8.
>
>
>
> Does someone have any idea what else I should try to do to resolve it?
> Here is the error message. The nonmem code and data are quite long and
> I could send you the code/data as files if requested. Many many thanks
> in advance for your kind help.
>
>
>
> NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE.
> NO. OF REQUIRED SIGNIFICANT DIGITS IN SOLUTION VECTOR
> TO DIFFERENTIAL EQUATIONS, 6, MAY BE TOO LARGE.
> MESSAGE ISSUED FROM SIMULATION STEP
>
>
>
>
>
> Best
>
>
>
>
>
> Thank you very much and best regards!
>
>
>
> *Penny (Peijuan) Zhu, Ph.D.*
>
>
>
> PD Bio-Pharma CDMA
>
> Sandoz
>
> 1N025, 100 College Road West
>
> Princeton, NJ 08540
>
>
>
>
>
>
>
> -- Sam Liao Pharmax Research Inc. 14 Upland, Irvine, CA 92602 Phone:
> 201-9882043 efax: 720-2946783 www.pharmaxresearch.com
> <http://www.pharmaxresearch.com>
>
Received on Thu Jan 05 2017 - 11:32:49 EST

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