Hi Brady, If you want to include (circadian) rhythms in the production (or elimination) of your endogenous substance, there are also other considerations. One is 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 system, which you can either do at the earliest observation using eqns (like Bill suggested), or just start the system at its average value 24 h before your first observation and let the system run. The latter is sometimes simpler when the analytic solutions to complex rhythm patterns become too intricate.
Best regards, Mats 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 www.farmbio.uu.se/research/researchgroups/pharmacometrics/<http://www.farmbio.uu.se/research/researchgroups/pharmacometrics/> From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Paolo Denti Sent: Wednesday, May 27, 2015 7:52 AM To: Moffett, Brady S.; nmusers@globomaxnm.com Subject: Re: [NMusers] RE: Dataset coding for baseline endogenous substance Hi Brady, for actual code examples and methods to introduce error or estimate you baseline, I would suggest looking into this paper. C. Dansirikul, H. E. Silber, and M. O. Karlsson, "Approaches to handling pharmacodynamic 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. Regards, Paolo On 2015/05/27 01:01, Denney, William S. wrote: Hi Brady, Generally, you will just include the baseline measurement as time=0 and then reference all other times from that time. So, if your baseline value was drawn at 8AM on day 1 while the first dose was at 10AM, just set the baseline 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 important part is that you want the time between baseline and the next measurement 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 endogenous >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, but you will >solve the equations for A_0 being steady-state and set it to the steady-state >value. Thanks, Bill From: owner-nmus...@globomaxnm.com<mailto:owner-nmus...@globomaxnm.com> [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Moffett, Brady S. Sent: Tuesday, May 26, 2015 6:02 PM To: nmusers@globomaxnm.com<mailto:nmusers@globomaxnm.com> 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 endogenous substances, but nothing on how to incorporate the baseline endogenous substance value (DV) into the dataset. The data is from clinical use, and the baseline values are not drawn at exactly the same times prior to drug administration. Any assistance would be appreciated! Thank you in advance... Brady S Moffett, PharmD, MPH ______________________________________________________________________ CONFIDENTIALITY NOTICE: The information in this e-mail may be confidential and/or privileged. If you are not the intended recipient or an authorized representative of the intended recipient, you are hereby notified that any review, dissemination, or copying of this e-mail and its attachments, if any, or the information contained herein is prohibited. If you have received this e-mail in error, please immediately notify the sender by return e-mail and delete this e-mail from your computer system. Thank you. ______________________________________________________________________ -- ------------------------------------------------ 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.de...@uct.ac.za<mailto:paolo.de...@uct.ac.za> ------------------------------------------------ ________________________________ UNIVERSITY OF CAPE TOWN This e-mail is subject to the UCT ICT policies and e-mail disclaimer published on our website at http://www.uct.ac.za/about/policies/emaildisclaimer/ or obtainable from +27 21 650 9111. This e-mail is intended only for the person(s) to whom it is addressed. If the e-mail has reached you in error, please notify the author. If you are not the intended recipient of the e-mail you may not use, disclose, copy, redirect or print the content. If this e-mail is not related to the business of UCT it is sent by the sender in the sender's individual capacity.
