Dear NMusers,
Currently, I'm working on a project in which ceftriaxone measurements have
been done for the free fraction and the total concentration. As both have
been measured (almost) simultaneously, we've specified these as L2 records
in our dataset. However, in a few records it occurs that one of the
measurements (within one L2 record) may be below the LLOQ. Therefore, we've
also included the M3 method to manage such measurements optimally.[1]
Unfortunately, NONMEM is giving the following error:
0PROGRAM TERMINATED BY OBJ2
WITH INDIVIDUAL 2 ID= 2.00000000000000E+00
NONZERO VALUE OF F_FLAG CAN NOT BE USED WITHIN
A MULTIPLE OBSERVATION L2 RECORD
It seems that you cannot specify a F_FLAG of 1 within one of the L2
records. Therefore, the M3 method cannot be applied simultaneously with L2
records in your dataset.
Although I can understand why this error occurs, I would like to know if
there is a way to include both methods. We try to solve for the
autocorrelation that may exist between the free (unbound) and the total
concentration of ceftriaxone.
Looking forward to receiving any answers/comments!
Kind regards,
*Dr. T. Preijers PharmD, PhD *
*Hospital Pharmacist and Clinical Pharmacologist *
Hospital Pharmacy
Erasmus MC Rotterdam
[1] Ahn JE, Karlsson MO, Dunne A, Ludden TM. Likelihood based approaches to
handling data below the quantification limit using NONMEM VI. J
Pharmacokinet Pharmacodyn. 2008 Aug;35(4):401-21.
Combining L2-records configuration with M3 method
One simplistic solution would of course be to change the L2 variable so that if
one (or both) in a pair of observations is BLQ, then the L2 values are set to
different values, to ignore the correlation between the two analytes.
Since you only have a few BLQ records, perhaps this can be acceptable?
Best regards
Jakob
Jakob Ribbing, Ph.D.
Principal Consultant, Pharmetheus AB
Cell/Mobile: +46 (0)70 514 33 77
[email protected]
www.pharmetheus.com
Phone, Office: +46 (0)18 513 328
Uppsala Science Park, Dag Hammarskjölds väg 36B
SE-752 37 Uppsala, Sweden
Quoted reply history
> On 19 Dec 2023, at 08:50, T. Preijers <[email protected]> wrote:
>
> Dear NMusers,
>
> Currently, I'm working on a project in which ceftriaxone measurements have
> been done for the free fraction and the total concentration. As both have
> been measured (almost) simultaneously, we've specified these as L2 records in
> our dataset. However, in a few records it occurs that one of the measurements
> (within one L2 record) may be below the LLOQ. Therefore, we've also included
> the M3 method to manage such measurements optimally.[1]
>
> Unfortunately, NONMEM is giving the following error:
> 0PROGRAM TERMINATED BY OBJ2
> WITH INDIVIDUAL 2 ID= 2.00000000000000E+00
> NONZERO VALUE OF F_FLAG CAN NOT BE USED WITHIN
> A MULTIPLE OBSERVATION L2 RECORD
>
> It seems that you cannot specify a F_FLAG of 1 within one of the L2 records.
> Therefore, the M3 method cannot be applied simultaneously with L2 records in
> your dataset.
>
> Although I can understand why this error occurs, I would like to know if
> there is a way to include both methods. We try to solve for the
> autocorrelation that may exist between the free (unbound) and the total
> concentration of ceftriaxone.
>
> Looking forward to receiving any answers/comments!
>
> Kind regards,
>
> Dr. T. Preijers PharmD, PhD
> Hospital Pharmacist and Clinical Pharmacologist
> Hospital Pharmacy
> Erasmus MC Rotterdam
>
> [1] Ahn JE, Karlsson MO, Dunne A, Ludden TM. Likelihood based approaches to
> handling data below the quantification limit using NONMEM VI. J Pharmacokinet
> Pharmacodyn. 2008 Aug;35(4):401-21.
>
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