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: [email protected] [mailto:[email protected]] Sent: Wednesday, January 04, 2017 3:33 PM To: Zhu, Penny <[email protected]> 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, [email protected]<mailto:[email protected]> 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>
