could you show equations? Bioavailability is treated differently in
Nonmem and R, so code should reflect it.
On 2/11/2020 3:52 AM, Le Louedec Felicien wrote:
Dear NONMEM users,
I’m struggling for a couple of weeks against contradictory results
between NONMEM and R analysis of the same data with the same model which
includes a time-varying bioavailability. Here is a simplified example of
On the one hand, let’s introduce a bicompartmental model with a depot
compartment, where bioavailability is decreasing over time given a
maximum in decrease (MAXDECR) and a first-order decay constant (LAMBDA).
Instead of the variable TIME, I use a covariate TOLD (Time Of Last Dose)
in order to be sure that the value of F1 computed by NONMEM will be
independent of the time used for computation:
$INPUT CID TIME EVID AMT CMT DV MDV TOLD
$MODEL COMP=(DEPOT) COMP=(CENTRAL) COMP=(PERIPH)
MAXDECR = THETA(1)
LAMBDA = THETA(2) / 24 ; TIME is in hour, Lambda in day-1
F1 = 1 - MAXDECR + MAXDECR * EXP(-LAMBDA * TOLD)
(0, 0.5, 1) FIX
(0, 0.15 ) FIX
On the other hand, we have a dataset of 28 IDs with:
-the same dosing regimen of 400 mg qd for 28 days (one line with EVID=1
per administration, no ADDL).
-different “sampling occasions” at 0h, 6h, 12 and 18h post-dose; at day
1 for ID1, at day 1&2 for ID2, at day 1&2&3 for ID3, and so on until
ID28 who has a complete PK exploration from day 1 to 28. All these lines
are filled with EVID=0, DV=., and MDV=1.
Then, I estimate these concentrations in maximum a posteriori Bayesian
manner (MAXEVAL = 0) with ADVAN 13 (there is no inter-individual nor
My problem is that NONMEM found different concentrations in these 28
individuals, even though they received the same dose. Besides, as
excepted, I found that all individuals had the same value for F1 (at a
given time point).
Would any of you have an idea of why NONMEM does not return the same
Thank you very much in advance
Félicien LE LOUEDEC, PharmD
Centre de Recherches en Cancérologie de Toulouse (CRCT), Toulouse, FRANCE
Team 14: « Dose Individualization of Anticancer Drugs »
+335 31 15 55 69