From: Jose Molto jmolto@ns.hugtip.scs.es
Subject: [NMusers] RE: steady state dosing
Date: Tuesday, April 13, 2004 2:52 AM
Hello everyone,
I am starting to work with NONMEM and I would appreciate very much some
help from the forum.
I am trying to build a pharmacokinetic model for an oral drug which is
administered every 12 hours using a monocompartimental model (ADVAN2
TRANS2)
Subjects are receiving the drug for at least 4 weeks (so steady state is
assumed). Theoretically, they come to our unit in the morning, before
taking any medication. A first blood sample is drawn just before taking
the morning dose, and several blood samples are drawn during the following
12 hours (until the afternoon dose).
I would like to have some opinions regarding several isues:
1. If the steady-state is assumed, the SS item in the drug administration
events should be typed 1 or 2?
2. Blood samples are not drawn exactly 12 hours after the last dose (eg; a
patient may take the last dose -the day before- at 22:00, the first sample
is drawn at 8:00, and the morning dose is administered at 8:05). My
question is: Is correct if I consider that both doses were at SS with an
interdose interval (II) of 12 hours??? If not, how should I enter the data
in the data file?.
Thank you in advance,
Jos Molt, MD
"Lluita contra el Sida" Foundation
HIV Unit. H. Germans Trias i Pujol
Carretera de Canyet s/n
08916 Badalona. Barcelona
Telf: +34 93 497 88 87
Fax: +34 93 465 76 02
E-mail: jmolto@ns.hugtip.scs.es
steady state dosing
From: Bachman, William (MYD) bachmanw@iconus.com
Subject: RE: [NMusers] RE: steady state dosing
Date: Tue, April 13, 2004 8:42 am
As always, there is more than one day to do this. What I would do is:
1. code steady state dosing representing the bulk of the dosing during the
four weeks with one dose event record (SS=1, II=12) and coded at a time
prior to the 22:00 dose. 10:00 on the same day as the 22:00 dose seems
plausible. On second thought, just coding the 22:00 dose as a steady state
event (SS=1, II=12) should be sufficiently accurate.
2. code the dose taken at 22:00 as a non-steady state dose (SS=0, II=0) as
accurately as possible (with respect to time).
3. code the observation at 8:00 as accurately as possible (with respect to
time).
4. code any other doses and observations on the same day (as the first
observation) as non-steady state events. e.g. the dose at 8:05 and any
other samples taken at their respective times.
5. if another long interval occurs between sampling, code in a similar
manner: steady state dose to maintain the levels at steady state, then
non-steady state dose events during the sampling period if the doses are not
given at regular intervals and use accurate times for these doses and
samples.
Bill
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