Colleagues
I have encountered a problem during NONMEM execution.
Most subjects are dosed daily but a small number of subjects have large
intervals (> 30 days) between successive doses.
For subjects dosed daily, concentrations 24 hours after a dose are BQL and
there is no evidence of accumulation.
For the problem subjects, NONMEM either:
1. aborts (despite a NOABORT option) with an error message at the first dose
after the lengthy gap
2. or sends the following error message:
0PRED EXIT CODE = 1
0INDIVIDUAL NO. 103 ID= 3.11040000000000E+04 (WITHIN-INDIVIDUAL) DATA
REC NO. 56
THETA=
1.66E+02 1.15E-01 2.95E+01 1.81E+01 4.33E+01 3.01E+02 8.26E+00
0.00E+00 1.00E+00 0.00E+00
0.00E+00 1.00E+00 1.00E+00 1.00E+00 1.00E+00 1.00E+00 1.00E+00
OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0
NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE.
MAXIMUM NO. OF EVALUATIONS OF DIFFERENTIAL EQUATIONS, 1000000, EXCEEDED.
The error occurs with METHOD=1 but NOT with METHOD=0.
For one subject in whom doses were administered on Days 1, 30, and 60 (followed
by daily dosing), I deleted the first two dosing records and the error no
longer occurs with METHOD=1. I speculate that the error might relate to the
predicted concentration becoming Infinitesimally small after a lengthy interval
between doses, However, I have no idea if this is the explanation. And I am
reluctant to change the dataset so I seek other solutions.
Any ideas as to an explanation or a work-around?
Dennis
Dennis Fisher MD
P < (The "P Less Than" Company)
Phone / Fax: 1-866-PLessThan (1-866-753-7784)
www.PLessThan.com
