RE: [NMusers] Estimation of Intake Time

From: Gopalakrishnan, Mathangi <mgopalakrishnan_at_rx.umaryland.edu>
Date: Thu, 18 Jun 2015 16:00:42 +0000

Dear Andrezj,

You could consider using a shifted lag time parameter and then estimating t=
he between subject variability (BSV) on this lag time parameter to account =
for the uncertainty in the dosing time.

You then, would have to shift the current dosing times and time of drug coc=
nentrations by 12 hrs.

Thanks.

Mathangi Gopalakrishnan, MS, PhD
Center fro Translational Medicine,
UMB
www.ctm.umaryland.edu<http://www.ctm.umaryland.edu>

From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On=
 Behalf Of Andrzej Bienczak
Sent: Thursday, June 18, 2015 9:36 AM
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Estimation of Intake Time

Dear NMusers,

I would like to present you with a problem that some of you might have face=
d before. I am currently building a PK model for a drug with once daily ora=
l administration. The drug has a long half-life and can be taken either in =
the morning or at night. Unfortunately due to lack of consistency in the re=
cording of the administration times by the study team part of the patients =
flagged to have taken the medication in the mornings were in fact taking it=
 at night (i.e. 08:25 corresponds to 20:25 the previous day). At this stage=
 there is no way of tracking back what the correct intake times were.

The data consists of 2 sparse measurements per patient and indeed looking a=
t individual profiles you can clearly see that some samples are from the el=
imination phase, indicating the drug was taken more than 12h prior. I could=
 correct the dataset based on an empirical judgement backed up by the visua=
l analysis but I was hoping there would be a more robust way.

Is there any way to put a THETA on the dosage time for those patients to le=
t NONMEM estimate a corrected administration time?

I tried simply adding an extra parameter on the intake time for those patie=
nts (placed the code in $PK):

IF(FLAG_AM.EQ.1) TIME=TIME-THETA(17)

But received the following error message:

AN ERROR WAS FOUND IN THE CONTROL STATEMENTS.

 AN ERROR WAS FOUND ON LINE 30 AT THE APPROXIMATE POSITION NOTED:
    IF(FLAG_AM.EQ.1) TIME=TIME-THETA(17)
                     X
 THE CHARACTERS IN ERROR ARE: TIME
236 DATA ITEM MAY NOT BE CHANGED WITH THIS VALUE OF ICALL.


I would be grateful for some suggestions on how to deal with this issue.

Regards,

Andrzej


Andrzej Bienczak
MSc, MPharm, DiplPharm
Pharmacometrics Group
Division of Clinical Pharmacology
Department of Medicine
University of Cape Town



Received on Thu Jun 18 2015 - 12:00:42 EDT

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