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

From: Zhu, Penny <penny.zhu_at_sandoz.com>
Date: Thu, 5 Jan 2017 15:44:37 +0000

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>
Received on Thu Jan 05 2017 - 10:44:37 EST

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