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
