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RE: RE: Dataset coding for baseline endogenous substance

From: Mats Karlsson <Mats.Karlsson>
Date: Wed, 27 May 2015 06:37:39 +0000

Hi Brady,

If you want to include (circadian) rhythms in the production (or eliminatio=
n) of your endogenous substance, there are also other considerations. One i=
s that you need to retain information about the clock time of your samples,=
 even those before start of therapy. The other is how to initialize the sys=
tem, which you can either do at the earliest observation using eqns (like B=
ill suggested), or just start the system at its average value 24 h before y=
our first observation and let the system run. The latter is sometimes simpl=
er when the analytic solutions to complex rhythm patterns become too intric=

Best regards,

Mats Karlsson, PhD
Professor of Pharmacometrics

Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala

Phone: +46 18 4714105
Fax + 46 18 4714003<http://www.farmb=>

From: owner-nmusers
 Behalf Of Paolo Denti
Sent: Wednesday, May 27, 2015 7:52 AM
To: Moffett, Brady S.; nmusers
Subject: Re: [NMusers] RE: Dataset coding for baseline endogenous substance

Hi Brady,
for actual code examples and methods to introduce error or estimate you bas=
eline, I would suggest looking into this paper.

C. Dansirikul, H. E. Silber, and M. O. Karlsson, "Approaches to handling ph=
armacodynamic baseline responses," J. Pharmacokinet. Pharmacodyn., vol. 35,=
 no. 3, pp. 269-283, Jun. 2008.

The appendix includes code and dataset examples, so it should be of help.


On 2015/05/27 01:01, Denney, William S. wrote:
Hi Brady,

Generally, you will just include the baseline measurement as time=0 and t=
hen reference all other times from that time. So, if your baseline value w=
as drawn at 8AM on day 1 while the first dose was at 10AM, just set the bas=
eline time as 0 and the first dose time as 2 (also assuming that your time =
is in hours). If baseline is taken far before the next time, the only impo=
rtant part is that you want the time between baseline and the next measurem=
ent to be more than ~5-fold the auto-correlation time of your system.

From there, you will estimate your A_0 values as you have seen other places=
. A general note that is not always covered in other discussions of endoge=
nous substance PK: You want to make sure that your equations work so that =
A_0 is at steady state (usually). Often, you will not directly set A_0, bu=
t you will solve the equations for A_0 being steady-state and set it to the=
 steady-state value.



From: owner-nmusers
Sent: Tuesday, May 26, 2015 6:02 PM
To: nmusers
Subject: [NMusers] Dataset coding for baseline endogenous substance

I am modeling a drug that is also an endogenous substance.

I have found quite a bit of information on modeling practices with endogeno=
us substances, but nothing on how to incorporate the baseline endogenous su=
bstance value (DV) into the dataset.

The data is from clinical use, and the baseline values are not drawn at exa=
ctly the same times prior to drug administration.

Any assistance would be appreciated! Thank you in advance...

Brady S Moffett, PharmD, MPH

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Paolo Denti, PhD

Pharmacometrics Group

Division of Clinical Pharmacology

Department of Medicine

University of Cape Town

K45 Old Main Building

Groote Schuur Hospital

Observatory, Cape Town

7925 South Africa

phone: +27 21 404 7719

fax: +27 21 448 1989

email: paolo.denti



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Received on Wed May 27 2015 - 02:37:39 EDT

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