Re: [NMusers] NONMEM 2 Compartment Zero Order Absorption

From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>
Date: Mon, 1 Oct 2018 11:27:50 -0400

you need to use ADVAN3, or
with ADAN 4 put the dose to CMT=2, define D2 (not D1) and assign and FIX KA

Leonid

On 10/1/2018 11:12 AM, Bishoy Hanna wrote:
> Hello all,
>
>
> I am currently trying to model data for a compound that is orally administered. A two compartment model with FIRST order oral absorption is not describing the data well (in my opinion). Consequently, I am attempting to model the data using the same two compartment model except with ZERO order absorption. I am under the impression that I am able to use ADVAN 4 TRANS 4 as well as a D1 = theta (1). I have included a rate = - 2 for my dosing records in my data set.
>
> My control stream is written as such:
> $INPUT ID DOSE DAY TIME=TAD NTPD DV AMT COH ADDL II MDV RATE EVID CMT LDV
> $SUBROUTINES ADVAN4 TRANS4
> $PK
> TVD1 = THETA(1)
> D1 = TVD1*EXP(ETA(1))
> TVCL=THETA(2)
> CL=TVCL*EXP(ETA(2))
> TVV2=THETA(3)
> V2=TVV2*EXP(ETA(3))
> TVQ = THETA(4)
> Q=TVQ*EXP(ETA(4))
> TVV3=THETA(5)
> V3=TVV3*EXP(ETA(5))
>
>
> However, I get the following error:
>
> WARNINGS AND ERRORS (IF ANY) FOR PROBLEM 1
> (WARNING 2) NM-TRAN INFERS THAT THE DATA ARE POPULATION.
> AN ERROR WAS FOUND IN THE CONTROL STATEMENTS.
>
> THE CHARACTERS IN ERROR ARE:
> KA
> 196 $PK: NO VALUE ASSIGNED TO A BASIC PK PARAMETER.
> NMtran failed. There is no output for model 1. Contents of FMSG:
>
> WARNINGS AND ERRORS (IF ANY) FOR PROBLEM 1
> (WARNING 2) NM-TRAN INFERS THAT THE DATA ARE POPULATION.
> AN ERROR WAS FOUND IN THE CONTROL STATEMENTS.
> THE CHARACTERS IN ERROR ARE:
> KA
> 196 $PK: NO VALUE ASSIGNED TO A BASIC PK PARAMETER.
>
>
>
> My question is whether I can utilize ADVAN 4 TRANS 4 to model zero order absorption for an oral administered drug (if so, how do I address the error listed above) OR if I have to utilize ADVAN 6?
>
>
>
> Thanks in advance for taking time out of your busy day to help!
>
> Regards,
> Bishoy Hanna
> Scientist
> Celgene Corporation
> 179 Passaic Avenue, S11- 2645A, Summit, NJ, 07901
> Phone: (908) 897 - 7733
>
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Received on Mon Oct 01 2018 - 11:27:50 EDT

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