An error when running a plasma/urine model in SS. Would you please help?

On 7/9/2024 2:41 PM, Abdelrahman Saqr wrote: > Dear Colleagues, > > I am encountering the following error when I run a model that includes plasma and urine data and SS data column =1. When I remove the urine data (modelling only the plasma data), the model runs without any error. > > When I drop the SS column (run a single dose or even with additional doses), the model runs without any error. > > When I have both the urine data and SS assigned as 1 or 3, I face the following error : > > MONITORING OF SEARCH: > > 0THE INPUT MATRIX IS SINGULAR. SOME OF THE DIAGONAL ELEMENTS OF THE UPPER > TRIANGULAR MATRIX U OF THE LU FACTORIZATION ARE CLOSE TO ZERO. > 0THE INPUT MATRIX IS SINGULAR. SOME OF THE DIAGONAL ELEMENTS OF THE UPPER > TRIANGULAR MATRIX U OF THE LU FACTORIZATION ARE CLOSE TO ZERO. > > 0PRED EXIT CODE = 1 > > 0INDIVIDUAL NO. 1 ID= 3.00200000000000E+03 (WITHIN-INDIVIDUAL) DATA REC NO. 1 > > THETA= > 8.60E+00 1.39E+01 1.78E+02 1.33E-01 1.00E+00 > OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0 > NUMERICAL DIFFICULTIES WITH INITIAL ESTIMATE OF STEADY-STATE SOLUTION. > DA MATRIX IS NOT INVERTIBLE AT A ZERO STATE VECTOR. > TRY SETTING INITIAL ESTIMATE USING SS=3. > > I appreciate your help with interpreting and fixing this error. > Thanks, > > -- > *Abdelrahman Saqr * > MS. Experimental and Clinical Pharmacology | University of Minnesota > PhD Candidate | Department ofExperimental and Clinical Pharmacology > College of Pharmacy | University of Minnesota > > www.linkedin.com/in/abdelrahman-saqr < http://www.linkedin.com/in/abdelrahman-saqr >

On Thu, Jul 11, 2024, 2:10 AM Leonid Gibiansky <[email protected]> wrote: > Could you show the code and the data sample? > It is possible that urine compartment does not have SS, as it does not > have elimination. It needs to be emptied time to time, and it could be > difficult to code SS of this system. To check, you may look on the urine > compartment concentrations with additional doses: do they converge to SS > to increase with time? > Leonid > > On 7/9/2024 2:41 PM, Abdelrahman Saqr wrote: > > Dear Colleagues, > > > > I am encountering the following error when I run a model that includes > > plasma and urine data and SS data column =1. > > When I remove the urine data (modelling only the plasma data), the model > > runs without any error. > > > > When I drop the SS column (run a single dose or even with additional > > doses), the model runs without any error. > > > > When I have both the urine data and SS assigned as 1 or 3, I face the > > following error : > > > > MONITORING OF SEARCH: > > > > 0THE INPUT MATRIX IS SINGULAR. SOME OF THE DIAGONAL ELEMENTS OF THE UPPER > > TRIANGULAR MATRIX U OF THE LU FACTORIZATION ARE CLOSE TO ZERO. > > 0THE INPUT MATRIX IS SINGULAR. SOME OF THE DIAGONAL ELEMENTS OF THE UPPER > > TRIANGULAR MATRIX U OF THE LU FACTORIZATION ARE CLOSE TO ZERO. > > > > 0PRED EXIT CODE = 1 > > 0INDIVIDUAL NO. 1 ID= 3.00200000000000E+03 (WITHIN-INDIVIDUAL) > > DATA REC NO. 1 > > THETA= > > 8.60E+00 1.39E+01 1.78E+02 1.33E-01 1.00E+00 > > OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0 > > NUMERICAL DIFFICULTIES WITH INITIAL ESTIMATE OF STEADY-STATE SOLUTION. > > DA MATRIX IS NOT INVERTIBLE AT A ZERO STATE VECTOR. > > TRY SETTING INITIAL ESTIMATE USING SS=3. > > > > I appreciate your help with interpreting and fixing this error. > > Thanks, > > > > -- > > *Abdelrahman Saqr * > > MS. Experimental and Clinical Pharmacology | University of Minnesota > > PhD Candidate | Department ofExperimental and Clinical Pharmacology > > College of Pharmacy | University of Minnesota > > www.linkedin.com/in/abdelrahman-saqr > > http://www.linkedin.com/in/abdelrahman-saqr > > > >

On 7/15/2024 3:01 PM, Abdelrahman Saqr wrote: > Thank you all for your help. > > Yes, that is what I believed in. The urine compartment is the problem. I tried the empirical steady state method (ADDL = -ve integer) with the plasma data only and then with the urine. The plasma achieves SS after a few number of doses; however, the urine compartment does not even with a very large number of doses. And I think this is as Saeheum has mentioned due to the emptying process. > > I did use the EVID to empty out the urine compartment (EVID = -v integer). > > I am not sure if there is a way in NONMEM to select compartments to be tested for the SS. (i.e. the central compartment is tested for SS but the output compartment is ignored) > > C ID TIME TAD AMT AMT_MOLAR AMT_MPA AMT_MPA_MOL RATE DV DV_MOLAR DV_AMT_MOL LN_DV_AMT_MOL Uvol CMT EVID MDV L2 ADDL II SS DVID DATE 0 1 19:30:00 -24 500 0 369.5 1.153606 -1 0 0 0 0 0 1 1 1 0 0 0 1 0 4/4/2018 0 1 19:30:00 -12 500 1.153403 369.5 1.153606 0 0 0 0 0 0 1 1 1 0 0 0 0 0 4/4/2018 > > 0 1 8:08:00 0 0 0 0 0 0 2007 6.266001 6.266001 6.266001 0 2 0 0 1 0 0 0 1 4/5/2018 0 1 8:08:00 0 500 1.153403 369.5 1.153606 0 0 0 0 0 0 1 1 1 0 0 0 0 0 4/5/2018 > > 0 1 8:08:00 0 0 0 0 0 0 0 0 0 0 0 4 2 1 11 0 0 0 3 4/5/2018 0 1 8:36:00 0.5 0 0 0 0 0 17010 53.10646 53.10646 53.10646 0 2 0 0 2 0 0 0 1 4/5/2018 0 1 9:08:00 1 0 0 0 0 0 21791 68.03309 68.03309 68.03309 0 2 0 0 3 0 0 0 1 4/5/2018 0 1 10:06:00 2 0 0 0 0 0 6373 19.89697 19.89697 19.89697 0 2 0 0 7 0 0 0 1 4/5/2018 0 1 11:08:00 3 0 0 0 0 0 4461 13.92757 13.92757 13.92757 0 2 0 0 8 0 0 0 1 4/5/2018 0 1 12:07:00 4 0 0 0 0 0 3867 12.07306 12.07306 12.07306 0 2 0 0 9 0 0 0 1 4/5/2018 0 1 13:07:00 5 0 0 0 0 0 7404 23.11583 23.11583 23.11583 0 2 0 0 10 0 0 0 1 4/5/2018 0 1 14:10:00 6 0 0 0 0 0 5256 16.40962 16.40962 16.40962 0 2 0 0 11 0 0 0 1 4/5/2018 0 1 14:10:00 6 0 0 0 0 0 3396 10.60256 4665.126 8.44787 440 -4 0 0 600 0 0 0 3 4/5/2018 0 1 14:10:00 6 0 0 0 0 0 0 0 0 0 0 4 2 1 6 0 0 0 3 4/5/2018 0 1 15:10:00 7 0 0 0 0 0 3318 10.35904 10.35904 10.35904 0 2 0 0 12 0 0 0 1 4/5/2018 0 1 16:10:00 8 0 0 0 0 0 4235 13.22198 13.22198 13.22198 0 2 0 0 13 0 0 0 1 4/5/2018 0 1 17:08:00 9 0 0 0 0 0 6954 21.7109 21.7109 21.7109 0 2 0 0 14 0 0 0 1 4/5/2018 0 1 18:08:00 10 0 0 0 0 0 7505 23.43116 23.43116 23.43116 0 2 0 0 4 0 0 0 1 4/5/2018 0 1 19:08:00 11 0 0 0 0 0 2390 7.461755 7.461755 7.461755 0 2 0 0 5 0 0 0 1 4/5/2018 0 1 20:08:00 12 0 0 0 0 0 20163 62.95036 11834.67 9.378788 188 -4 0 0 1200 0 0 0 3 4/5/2018 0 1 20:10:00 12 0 0 0 0 0 1316 4.108648 4.108648 4.108648 0 2 0 0 6 0 0 0 1 4/5/2018 > > On Thu, Jul 11, 2024 at 8:28 AM Saeheum Song < [email protected] < mailto: [email protected] >> wrote: > > There is no steady state in urine. Urine is always accumulating and > empty out. You can set ss to the central compartment. After setting > ss to the central compartment, you need to empty and reset urine > compartment using evid. > > On Thu, Jul 11, 2024, 2:10 AM Leonid Gibiansky > <[email protected] <mailto:[email protected]>> wrote: > > Could you show the code and the data sample? > It is possible that urine compartment does not have SS, as it > does not > have elimination. It needs to be emptied time to time, and it > could be > difficult to code SS of this system. To check, you may look on > the urine > compartment concentrations with additional doses: do they > converge to SS > to increase with time? > Leonid > > On 7/9/2024 2:41 PM, Abdelrahman Saqr wrote: > > Dear Colleagues, > > > > I am encountering the following error when I run a model that > includes > > plasma and urine data and SS data column =1. > > When I remove the urine data (modelling only the plasma > data), the model > > runs without any error. > > > > When I drop the SS column (run a single dose or even with > additional > > doses), the model runs without any error. > > > > When I have both the urine data and SS assigned as 1 or 3, I > face the > > following error : > > > > MONITORING OF SEARCH: > > > > 0THE INPUT MATRIX IS SINGULAR. SOME OF THE DIAGONAL ELEMENTS > OF THE UPPER > > TRIANGULAR MATRIX U OF THE LU FACTORIZATION ARE > CLOSE TO ZERO. > > 0THE INPUT MATRIX IS SINGULAR. SOME OF THE DIAGONAL ELEMENTS > OF THE UPPER > > TRIANGULAR MATRIX U OF THE LU FACTORIZATION ARE > CLOSE TO ZERO. > > > > 0PRED EXIT CODE = 1 > > > 0INDIVIDUAL NO. 1 ID= 3.00200000000000E+03 (WITHIN-INDIVIDUAL) > > > DATA REC NO. 1 > > THETA= > > 8.60E+00 1.39E+01 1.78E+02 1.33E-01 1.00E+00 > > OCCURS DURING SEARCH FOR ETA AT INITIAL VALUE, ETA=0 > > NUMERICAL DIFFICULTIES WITH INITIAL ESTIMATE OF > STEADY-STATE SOLUTION. > > DA MATRIX IS NOT INVERTIBLE AT A ZERO STATE VECTOR. > > TRY SETTING INITIAL ESTIMATE USING SS=3. > > > > I appreciate your help with interpreting and fixing this error. > > Thanks, > > > > -- > > *Abdelrahman Saqr * > > MS. Experimental and Clinical Pharmacology | University of > Minnesota > > PhD Candidate | Department ofExperimental and Clinical > Pharmacology > > College of Pharmacy | University of Minnesota > > www.linkedin.com/in/abdelrahman-saqr > http://www.linkedin.com/in/abdelrahman-saqr > > http://www.linkedin.com/in/abdelrahman-saqr http://www.linkedin.com/in/abdelrahman-saqr> > > > > -- > *Abdelrahman Saqr * > MS. Experimental and Clinical Pharmacology | University of Minnesota > PhD Candidate | Department ofExperimental and Clinical Pharmacology > College of Pharmacy | University of Minnesota > > www.linkedin.com/in/abdelrahman-saqr < http://www.linkedin.com/in/abdelrahman-saqr >