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Dear Members,
I have a problem related to data input in WinNonlin for estimation of
metabolite kinetics. I have an intravenously administered drug 'X'
that follows two compartment model with Michaelis-Menten elimination.
It also gets converted into a metabolite 'Y' in plasma and 'Y' follows
one compartmental model. So, I have three equations to describe the
whole process.
1) Drug concentration in central compartment or plasma, 2) Metabolite
concentration in plasma, 3) Drug concentration in peripheral
compartment.
Hence I have THREE functions that describes the above THREE equations.
I have Time, Drug concentration in plasma, and Metabolite
concentration in plasma. When assigning data variables in WinNonlin, I
assign Time to X-axis. The problem is assigning Y-axis. I can only
assign either Drug Conc. or Metabolite Conc to Y-axis as there is only
one Y-axis.
The data is as follows:
Time Drug Conc Metabolite Conc
(min) (ng/mL) (ng/mL)
10 108.15 6.58
20 68.5 10.95
30 50.55 12.06
45 44.15 14.35
60 37.56 12.80
90 32.26 11.48
120 27.19 9.86
150 20.56 6.46
180 13.55 4.12
Please suggest me how to input all the data for user specified model.
(I have also tried using 'Function' variable in data variables. I
assigned drug concentration in plasma to 'Function 1' and metabolite
concentration in plasma to 'Function 2'. But again, as I have three
functions this option is also not working)
Thanks & Regards
Sivacharan Kollipara
Metabolism & Pharmacokinetics Department
Ranbaxy Research Laboratories
India
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The following message was posted to: PharmPK
Dear Sivacharan
You can try noncompartmental model, I think it best fits in to that.
You are saying the drug would be analyzed best by two compartment
model and metabolite by one compartment model but it is other way
around when I looked at your data.
Dr.Srinivas Rao
New Chemical Entity Research
Lupin Research Park
46A/47A, Village: Nande, Taluka: Mulshi
Pune-411 042, India
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Dear Sivacharan,
I think you should not have trouble using Function variable 1,2,3 for
each of plasma conc data. When you say " this option is not working"
do you get any specific error message?
Best
Ganesh
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[The alignment/format of the table may have altered during email
transmission, it looks like 'Metabolite' belongs on the end of the
line above under Analyte - db]
The following message was posted to: PharmPK
Dear Sivacharan,
To use your data with a multiple-function user model in WinNonlin, the
easiest way to do this is to "stack" your data. That is to say, place
all of the concentration data into one column. Using your example, the
data could be arranged as follows:
Time Conc Function Analyte
(min) (ng/mL)
10 108.15 1 Parent
20 68.5 1 Parent
30 50.55 1 Parent
45 44.15 1 Parent
60 37.56 1 Parent
90 32.26 1 Parent
120 27.19 1 Parent
150 20.56 1 Parent
180 13.55 1 Parent
10 6.58 2 Metabolite
20 10.95 2 Metabolite
30 12.06 2 Metabolite
45 14.35 2 Metabolite
60 12.80 2 Metabolite
90 11.48 2 Metabolite
120 9.86 2 Metabolite
150 6.46 2 Metabolite
180 4.12 2 Metabolite
In the WinNonlin model, under Data Variables, specify Time = X, Conc
Y, and drag Function to the function box. The Analyte column is a
descriptor; it is not required, but could be put in the Carry Along box
to make interpretation of results easier. In the user model code,
function 1 would correspond to the two-compartment model for the Parent,
and function 2 would correspond to the one-compartment model for the
metabolite.
Sincerely,
Pharsight Software Support
Email: support.at.pharsight.com
Web: http://www.pharsight.com/support/support_home.php
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