Is �DOSE=0� accepted by NONMEM?

4 messages 4 people Latest: Sep 08, 2015

Is �DOSE=0� accepted by NONMEM?

From: Zheng Liu Date: September 07, 2015 technical
Dear NONMEM users, I have a group of patients, whose plasma drug levels are measured and known at time=0 (no further drug is given to the patients afterwards.). I try to know, after how long time the drug will be completely cleared out from these patients. Naturally I used NONMEM to fit the patients' V and CL, in order to get plasma concentration change profile. However seems NONMEM only accepts DOSE is a positive number. If DOSE=0, NONMEM can't perform the fitting. Can anyone kindly give me some suggestions to solve this problem? Thanks a lot in advance! PTID DV AMT time EVID 2 . 0 0 1 2 6.8 0 0 0 2 1.1 0 3 0 2 0 0 6 0 3 . 0 0 1 3 1.08 0 0 0 3 0.16 0 3 0 3 0.03 0 6 0 3 0 0 9 0 Zheng

Re: Is �DOSE=0� accepted by NONMEM?

From: Paolo Denti Date: September 07, 2015 technical
Dear Zheng, NONMEM wants an amount there, or it won't interpret that record as a dose. On the other hand, if you don't put anything into the system, or you do not initialise the compartments (see below), nothing is going to happen. If you want to use a dose to initialise the system, them you can put AMT= 1 and use the bioavailability parameter to decide how much to put it F1= YYY. YYY can be then be a number in the data or a parameter. If you want to use parameters, I suggest that you look into how to model baselines Dansirikul C, Silber HE, Karlsson MO. 2008. Approaches to handling pharmacodynamic baseline responses. J. Pharmacokinet. Pharmacodyn. 35:269283. In the same paper there are also snippets of code on how to initialise compartments with the command A_0(1) = YYY which is a somewhat neater option. I would prefer the second option A_0_1, but I guess if you use some of the basic ADVANs, NONMEM may expect a dose and give you an error if it doesn't find one. Good luck. Paolo
Quoted reply history
On 2015/09/07 08:30, Zheng Liu wrote: Dear NONMEM users, I have a group of patients, whose plasma drug levels are measured and known at time=0 (no further drug is given to the patients afterwards.). I try to know, after how long time the drug will be completely cleared out from these patients. Naturally I used NONMEM to fit the patients' V and CL, in order to get plasma concentration change profile. However seems NONMEM only accepts DOSE is a positive number. If DOSE=0, NONMEM can't perform the fitting. Can anyone kindly give me some suggestions to solve this problem? Thanks a lot in advance! PTID DV AMT time EVID 2 . 0 0 1 2 6.8 0 0 0 2 1.1 0 3 0 2 0 0 6 0 3 . 0 0 1 3 1.08 0 0 0 3 0.16 0 3 0 3 0.03 0 6 0 3 0 0 9 0 Zheng -- ------------------------------------------------ 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_at_uct.ac.za<mailto:paolo.denti_at_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.

Re: Is �DOSE=0� accepted by NONMEM?

From: Paul Matthias Diderichsen Date: September 08, 2015 technical
On 9/7/2015 8:30, Zheng Liu wrote: > However seems NONMEM only accepts DOSE is a positive number. If DOSE=0, > NONMEM can't perform the fitting. Can anyone kindly give me some > suggestions to solve this problem? Thanks a lot in advance! You could set EVID=2 instead of 1 in the records with TIME=0 and AMT=0. -- Paul Matthias Diderichsen, PhD Quantitative Solutions B.V. +31 624 330 706

Re: Is �DOSE=0� accepted by NONMEM?

From: Leonid Gibiansky Date: September 08, 2015 technical
Zheng, If you have only subjects with unknown dosing history, one can assume mono-exponential decay (provided that the data do not contradict this assumption: can be checked by plots of DV vs TIME in semi-scale). With this assumption, one can use $PRED C0 = THETA(1)*EXP(ETA(1)) ; initial value K = THETA(2)*EXP(ETA(2)) ; rate of decay TY = C0*EXP(-K*TIME) ; individual prediction Y = TY*(1+EPS(1)) ; proportional error model Leonid -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566
Quoted reply history
On 9/7/2015 2:30 AM, Zheng Liu wrote: > Dear NONMEM users, > > I have a group of patients, whose plasma drug levels are measured and > known at time=0 (no further drug is given to the patients afterwards.). > I try to know, after how long time the drug will be completely cleared > out from these patients. Naturally I used NONMEM to fit the patients' V > and CL, in order to get plasma concentration change profile. > > > However seems NONMEM only accepts DOSE is a positive number. If DOSE=0, > NONMEM can't perform the fitting. Can anyone kindly give me some > suggestions to solve this problem? Thanks a lot in advance! > > PTID DV AMT time EVID > 2 . 0 > 0 1 > 2 6.8 0 0 0 > 2 1.1 0 3 0 > 2 0 0 6 0 > 3 . 0 0 1 > 3 1.08 0 0 0 > 3 0.16 0 3 0 > 3 0.03 0 6 0 > 3 0 0 9 0 > > > > Zheng