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Hello all,
Perhaps someone here can help...and no laughing all you NONMEM users ;)
I am using Kinetica v4 to model some PK data, and have a couple of
problems:
1. It seems that the compound's absorption may be zero order (and 2-
comp disposition). We have multiple dose data (a few points after the
1st dose, scattered troughs, and a full profile after the nth dose). The
compound is administered s.c. -so Tinf or ko need to be fitted
parameters. Of the “editable” available models (ie. .bas files) the
zero-order *single-dose* model is easily adapted to make Tinf a fitted
parameter (or replaced by ko and dose). Unfortunately, there are no
*multiple-dose* editable models (ie .bas files) available at all, of any
sort, either within Kinetica or on-line from Innaphase. I have tried to
modify the single-dose models, but met with little success.
I wouldn’t mind if there was the facility for me to open up the other
hard-coded *multiple-dose* models (eg. FitMultiMicroExtravascular) and
see how they are coded and adapt my re-vamped (ko, Dose) zero-order
single-dose model to multiple-dose...
2. Similarly I was considering moving on from PPharm to Kinetica to
model some *population* PK chronic oral dosing (tau=24) data at steady-
state with data available for only a single inter-dosing interval at
steady-state. In PPharm you could do this easily by setting the flag
SS=tau for the admin. However, in Kinetica v4 this is not available, nor
is there a dedicated model available. I guess I could insert a series
(several months worth) of bogus administrations before the dose after
which the data was obtained -but that would be tedious for lots of
subjects...again coding my own model (allowing for different tau values
for each subject) has proved difficult.
Again, there are no editable *population* models available (of any sort,
unless you count a couple of very simple examples in the manual) for me
to play with and see how they tick...
As someone here said before, if anyone could provide me with a model
file or two (or even some code that points in the right direction) there
is a beer in it for you here in Adelaide (but no return airfares!!).
Thanks,
David
David Foster, PhD
Department of Clinical and Experimental Pharmacology Faculty of Health
Sciences
Adelaide University
Adelaide, South Australia 5005
Email: david.foster.-at-.adelaide.edu.au
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The following message was posted to: PharmPK
David,
Using an earlier version of Kinetica, I was able to fit PK data observed
during a multiple dose regimen. I applied the following tricks :
- Prepare a Data file somewhat resembling a Nonmem file, e.g.:
X Dose Y1
h µg µg/L
0 16000
1 10.0017
2 6.6864
4.02 6.4792
6.02 6.272
24.47 16000
48.43 16000
72.15 16000
96.33 16000
120.3 16000
145.63 6.3938
145.8 16000
168.23 16000
192.38 16000
215.97 16000
218.38 25.8489
219.88 32.1586
220.18 25.0602
221.95 21.1166
- Use the "Designer" tool and build up a compartmental model based on
differential equations for your data; this will produce a standard
Pseudo-Basic module
- Edit this module : declare the Doses as a supplemental input value
Dim Dose as InputColumn
- Equate the amount in first (absorption) compartment to the first dose
(if the 1st dose is given at time 0) Z0 = Dose(1)
- Now in the loop "For i=1 To X_count", it is necessary to first
initialize all YNcalc as missing, so that this status is retained at
dosing times, when there is no observation : Y1calc(i) = -1 '
initialise to -1
Y1calc_status(i) = 3 ' declare the status of Missing Value When
observations are encountered in Y1, Kinetica will calculate an Y1calc
value and set its status code to Normal. (You may argue Kinetica should
do that by itself, but this is not the case, don't ask me why).
- Then, in this loop, add the subsequent doses at dosing times, after
the lines about YNcalc evaluation :
If Dose_status(i) = 0 then ' If there is a dosing,
Z0 = Z0 + Dose(i) ' Add the corresponding dose into the
End If ' absorption compartment
I hope this will help for your problem. But I agree with you about the
fact that easily editable models for non-standard situations are still
lacking in Kinetica, and programming remains tricky. Good luck
Thierry BUCLIN, MD
Lecturer, consulting physician and clinical researcher Division of
Clinical Pharmacology
University Hospital CHUV - Beaumont 633
CH 1011 Lausanne - SWITZERLAND
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)