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A colleague would like to analyze PK properties of an I125 labeled
peptide which he administered IV to mice. I'm still ascertaining all
the details of the information he has, but currently his data is
simply expressed as a % of input radioactivity in plasma as a
function of time. Is there a way to look at his data using WinNonLin
in the absence of other information or does one need information
about specific activity in order to convert to mass units? This is
clearly very preliminary data, but I would be interested also in
finding out how one typically uses WinNonLin for analysis of
radioactive data assuming one had access to all relevant information
(and what is that relevant information?)
Thanks so much,
Noelle
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Yes, you could use WinNonLin for the analysis and you might want to
express the data as concentration CPM/ml (count per minute/ml) rather
than % (depending on which PK parameters you want to estimate). Also
you need the dose (CPM) for the analysis. There is no need to convert
the data into mass (though you could do conversion in WinNonLin).
You could use either complied models or write your own custom model.
Hope this helps.
Best,
Nidal Al-Huniti, PhD
Senior Associate Scientific Consultant
Strategic Consulting Services
Pharsight Corporation
Office: 919-852-4640
nal-huniti.-a-.pharsight.com
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Dear Noelle,
Are you interested in the PK properties of the radioactivity or of
the peptide and using I125 as a tracer. Percent of injected dose of
radioactivity is probably the easiest to present and understand and
can be converted to mass units readily.
A little caution is advised in extrapolating the later time points as
they are corrected for radioactive decay and the weight is not
distributed as you would think. You may want to weight Y or y^2 and
in my experience 1/Y is not appropriate with decay corrected data.
I am attaching the Methods section from an abstract presentation of a
radiolabeled peptide:
"METHODS: Thirteen patients with clinical evidence or at high risk
for venous thrombosis, were administered ~20mCi Tc-99mP280 (~100ug
P280 peptide) and serial blood/plasma samples were taken at three
minutes and at increasing intervals to 24 hours. Resultant plasma/
urine radioactivity as Counts Per Minute (CPM)/ml was corrected for
radioactive decay to the time of administration. These data were fit
to a biexponential equation, CPM/ml(corrected)=A1Ce-81Ct + A2Ce-82Ct
using WinNonlin 1.1 (Scientific Consulting, Inc) with a weight of 1/y
and the resultant parameters analyzed as described in: Webster W. et
al, J Nucl Med 1992: 33:498-504. Urine clearance was determined as
the total radioactivity excreted in the urine, calculated by a
sigmoid E-max model, divided by the total plasma AUC. Data are
reported as the mean +/- SEM.
RESULTS and CONCLUSIONS: Data from the plasma tracer radioactivity as
CPM/ml is assumed to represent 99mTc-P280. The mean plasma terminal
elimination or beta half life for the 99mTc-P280 was 2.98+/-0.42
hours - 88.4+/-2.09% of the total plasma AUC was in the beta
elimination phase.. The distribution or " half life was 13.2+/-3.6
minutes. The corresponding effective half lives(corrected for both
radioactive decay and elimination) were 1.91+/-0.16 hours and 12.6
+/-3 minutes. The apparent volume of the central compartment was 10.4
+/-1.2 liters. The equilibrium or steady state volume of distribution
is 25+/-3.2 liters. The volume of the tissue compartment is 14.6
+/-2.1 liters.
The probability of an injected 99mTc-P280 molecule leaving the
central pharmacokinetic space was 75+/-3%. Those molecules eliminated
from the body, had a mean residence time of 3.76+/-0.5 hours. Those
molecules reaching the peripheral pharmacokinetic space had a mean
residence time of 2.96+/-0.5 hours. At any time the ratio of
molecules in the peripheral kinetic space was 20+/-4% of the total
body activity.
Renal clearance of 99mTc-P280 was 90+/-13.1ml/minute (74.2+/-5.7% of
total body clearance). Compared to the calculated creatinine
clearance of 70.9+/-6.7 ml/minute, the renal elimination exceeds the
filtration rate and therefore a portion of the renal elimination is
by active secretion or metabolism. "
William Webster, PharmD, FCCP, BCPS
Office: 727-363-0072
9525 Blind Pass Rd
Courageous 1001
St Pete Beach, FL 33706
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