Hi Mike,
Everything should work as you coded, no need to correct anything
Here is the story: SS code (dose) gives you the state of the system at
the time of that dose. After that, the system is on it's own, controlled
by the dosing history that you provide in the following records. If you
do want to predict SS oscillations beyond II (with the steady-state
dosing), you should give dose at TIME == II. If you want to skip the
dose (as you need to in your case) you skip it: computation will be done
correctly.
Guide is very specific way: indeed, to compute steady-state beyond II,
you need to add dose, and this dose should be additional (regular, not
steady-state) dose, same as SS dose.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
On 11/23/2010 5:26 PM, Dodds, Mike wrote:
All,
I've recently been working up a Phase 2 PK data set: oral
administration, QD dosing and PK samples on weeks 3, 5 and 7 of the
study. Per protocol, the morning dose is withheld and the patient comes
to the clinic for a blood sample. To me, this seems like a
straightforward application of SS and II, something like:
ID DATE TIME CMT DV EVID AMT SS II MDV
11101 3/30/2010 7:45 1 . 1 200 1 24 1
11101 3/31/2010 9:33 2 25.6 0 . . . 0
However, Guide V, section 8.2.8 indicates predictions can't be made
beyond the dosing time + II:
"Ordinarily, steady-state levels can only be predicted between t1 , the
time on the steady-state dose record, and t2 , the sum of t1 and the
interdose interval. If it is not only necessary to compute a
steady-state prediction between t1 and t2 , but also after t2 , then
there must also occur one or more non-steady-state dose records at t2 ,
t2+II , etc. with doses just like the steady-state dose. "
Here, the PK sample is taken after dosing + II. NONMEM 7.1.2 appears to
give me a prediction, but I'm suspicious of the results. I thought about
adding a very, very small transient dose at the II, but the language in
8.2.8 seems to indicate the dose needs be "just like the steady-state
dose", so that might not work.
* *Have others encountered this issue, and if so, what did you do to
work around the limitation?*
* *Can other shed some light on what predictions can't be made
beyond II, since transient equations can be mixed with SS equations?*
Warm Regards,
Mike Dodds
