`could you show equations? Bioavailability is treated differently in`

`Nonmem and R, so code should reflect it.`

Thanks Leonid

On 2/11/2020 3:52 AM, Le Louedec Felicien wrote:

Dear NONMEM users,I’m struggling for a couple of weeks against contradictory resultsbetween NONMEM and R analysis of the same data with the same model whichincludes a time-varying bioavailability. Here is a simplified example ofmy issue:On the one hand, let’s introduce a bicompartmental model with a depotcompartment, where bioavailability is decreasing over time given amaximum 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 beindependent of the time used for computation:--- $INPUT CID TIME EVID AMT CMT DV MDV TOLD $MODEL COMP=(DEPOT) COMP=(CENTRAL) COMP=(PERIPH) $PK MAXDECR = THETA(1) LAMBDA = THETA(2) / 24 ; TIME is in hour, Lambda in day-1 F1 = 1 - MAXDECR + MAXDECR * EXP(-LAMBDA * TOLD) $THETA (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=1per administration, no ADDL).-different “sampling occasions” at 0h, 6h, 12 and 18h post-dose; at day1 for ID1, at day 1&2 for ID2, at day 1&2&3 for ID3, and so on untilID28 who has a complete PK exploration from day 1 to 28. All these linesare filled with EVID=0, DV=., and MDV=1.Then, I estimate these concentrations in maximum a posteriori Bayesianmanner (MAXEVAL = 0) with ADVAN 13 (there is no inter-individual norresidual variability).My problem is that NONMEM found different concentrations in these 28individuals, even though they received the same dose. Besides, asexcepted, I found that all individuals had the same value for F1 (at agiven time point).Would any of you have an idea of why NONMEM does not return the samepredictions ?Thank you very much in advance Kind regards Félicien LE LOUEDEC, PharmD PhD student Centre de Recherches en Cancérologie de Toulouse (CRCT), Toulouse, FRANCE Team 14: « Dose Individualization of Anticancer Drugs » +335 31 15 55 69lelouedec.felic...@iuct-oncopole.fr<mailto:lelouedec.felic...@iuct-oncopole.fr>