RE: [NMusers] two compartment with nonlinear elimination

From: Abu Helwa, Ahmad Yousef Mohammad - abuay010 <ahmad.abuhelwa_at_mymail.unisa.edu.au>
Date: Wed, 9 Sep 2015 02:43:29 +0000

Hi Chiaying,

  Following on Ken’s email. The way I usually code infusion models is to put the actual RATE in the input data file. Then NONMEM, by defaults, would know the infusion time by having the AMT and RATE column in the dataset. Therefore, you don’t need to add a parameter for the duration in your code.

Best,

Sincerely,
Ahmad Abuhelwa, PhD Candidate
Australian Center for Pharmacometrics |P1-09| Playford Building
School of Pharmacy and Medical Sciences
University of South Australia- City East Campus
Adelaide, South Australia
Australia
Email: ahmad.abuhelwa_at_mymail.unisa.edu.au<mailto:ahmad.abuhelwa_at_mymail.unisa.edu.au>
Mobile: +61 413118743


From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Ken Luu
Sent: Wednesday, 9 September 2015 11:30 AM
To: Chiaying Lin <cylin292_at_gmail.com>; nmusers_at_globomaxnm.com
Subject: RE: [NMusers] two compartment with nonlinear elimination

Hi Chiaying,
I didn’t realize that you were using D1 and setting the RATE to -2. I personally haven’t coded it this way for an IV route (may others who have could chime in). I’ve seen D1 being estimated as a parameter in an extravascular model. My first inclination, without viewing your results in detail, is to provide the actual rate in the data file and remove D1. You may just get the same results but at least you can rule out that the problem is due to your existing parameterization.

Ken

From: Chiaying Lin [mailto:cylin292_at_gmail.com]
Sent: Tuesday, September 08, 2015 6:17 PM
To: Ken Luu; nmusers_at_globomaxnm.com<mailto:nmusers_at_globomaxnm.com>
Subject: Re: [NMusers] two compartment with nonlinear elimination

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?

#ID

TIME

AMT

NDV

LNDV

EVID

MDV

CMT

BW

AGE

DOSE

RATE

DUR

1

0

81.3

.

.

1

1

1

81.3

50

81.3

-2

1

1

0.25

4.8

1.568616

1

81.3

50

81.3

               .

1

1

1

18

2.890372

1

81.3

50

81.3

               .

1


2015-09-08 23:34 GMT+08:00 Ken Luu <KLuu_at_isisph.com<mailto: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> [mailto: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<mailto: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 quite 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 - 22:43:29 EDT

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