NONMEM Users Network Archive

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Re: [NMusers] two compartment with nonlinear elimination

From: Chiaying Lin <cylin292_at_gmail.com>
Date: Wed, 9 Sep 2015 09:17:24 +0800

Hi Ken,
It's given via iv infusion. The infusion rate (RATE) and ruraiton (DUR) are
included in the data file. I also have defined D1=DUR in the $PK block.
There is something wrong?

#IDTIMEAMTNDVLNDVEVIDMDVCMTBWAGEDOSERATEDUR1081.3..11181.35081.3-2110.254.8
1.568616181.35081.3 .111182.890372181.35081.3 .=
1

2015-09-08 23:34 GMT+08:00 Ken Luu <KLuu_at_isisph.com>:

> Chiaying,
>
>
>
> Your concentration-time profiles seem to suggest that there’s an
> absorption phase which was not accounted for in your model/control stream=
.
> What was the route of administration?
>
>
>
> Ken
>
>
>
> *From:* owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com=
]
> *On Behalf Of *Chiaying Lin
> *Sent:* Tuesday, September 08, 2015 7:57 AM
> *To:* nmusers_at_globomaxnm.com
> *Subject:* [NMusers] two compartment with nonlinear elimination
>
>
>
> Dear NMusers,
>
> I'm a NM beginner modeling for a monoclonal antibody. Below is 12
> subjects's individual predicted plot , it seems that nonlinear
> elimination (Michaelis-Menten) model can fit the data well. However, when
> running the control stream (two compartment models with linear and
> non-linear elimination), the resulting Q THETA SE% and OMEGA SE% are quit=
e
> large even thought successful minimization.From the Correlation Matrix ,=
 I
> find that THETA (1) (VMAX) and THETA(2) (KM)are highly correlated
> (9.67E-01). Another problem is the .fit file can't be produced.
>
>
>
> I have tried various error models and initial estimations, however, none
> had better improvement and often got error message (error 134
> or parameter estimate is near its boundary). Does re-parameterization
> helpful ? or need to change to other models?
>
>
>
> Any suggestions for solving the problems are highly appreciated.
>
>
>
> (control stream will be send in another e-mail)
>

Received on Tue Sep 08 2015 - 21:17:24 EDT

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