Back to the Top
Dear all,
Does anyone encounter this issue:
How to run PK calculation when the drug itself is the endogenous substance? Do we need to subtract
the basal level before going to run PK analysis? If the basal level (the concentration of the IL-15)
was less than 5% of the corresponding Cmax in the lowest dosing group (0.5 μg//kg), also need to do
it this way? Or is there any standard to assess that issue? The dosing materail was IL-15.
Thanks,
Jack
Back to the Top
Jack
A principle based approach would be to model the endogenous input rate.
The baseline (and continuing contribution to measured concs) can then be
predicted from this rate and the estimated clearance of the substance.
Nick
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
Back to the Top
Jack,
If the endogenous concentrations of IL-15 are LESS than 5% of Cmax when exogenous IL-15 is
administered even in the lowest dosing group, there is NO need to apply any subtraction.
This is based on current guidelines on bioequivalence that exclude carryover effects when the
concentrations of a drug in the second period of a bioequivalence study are <5% of Cmax measured in
that period.
On the contrary, If concentrations are above 5% of Cmax, the subject must be excluded from the
statistical analysis.
In your case, you might be asked how you came up with the <5% values and therefore, it might be a
good idea to check a FULL baseline AUC of IL-15 in each of the subjects to provide compelling
evidence that endogenous IL-15 concentrations are indeed always <5% of the Cmax observed after
administration of exogenous IL-15.
Best
Stefano
--
STEFANO PERSIANI, Ph.D.
Director
Translational Sciences and Pharmacokinetics Department
ROTTAPHARM BIOTECH
Rottapharm Biotech S.r.l.
Via Valosa di Sopra, 9
stefano.persiani.at.rottapharm.com
--
Typically, one should collect three pre-dose baseline concentrations, -48, -24 and 0 hours, average
these values, and subtract this value from all post-dose concentrations for each subject.
Doug Smith
Tucson, AZ
Doug Smith
[It might also be useful to collect sample within the 24 hour period to account for diurnal
variation - db]
--
Hi Jack,
I have encountered this issue several times and I have concluded that subtracting the basal level
from the concentration at every timepoint is the only logical way to handle it. If you don't correct
for the basal level, you will have significant deviation from the true pk profile (i.e single
compartment may appear as two compartments, estimates of AUC, half life etc will be wrong). One
note, if the concentration after subtracting the basal value is negative, this concentration should
obviously be zero, but it's not clear to me if all subsequent time points should be zero too or if
you can continue to adjust the values by subtracting the basal level. That would likely be the sign
of poor assay performance though.
Parag
prgkmr.-a-.gmail.com
--
Dear Jack,
For non-compartmental PK analysis, the basal level would be subtracted from the drug concentrations
to calculate the clearance and other PK parameters. I agree with Professor Holford's advice on PK
modeling of the drug.
Best regards,
Sam Liao, Ph.D.
Pharmax Research Inc.
Sam Liao
Back to the Top
Dear All:
I question arbitrary rules such as this about whether or not it is 5%. I question the word MUST.
I have no question about the issues involved, but I most certainly question rules such as 5% and
words such as MUST.
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D., F.C.P., F.A.A.C.P.
Professor of Medicine Emeritus,
Founder and Director Emeritus
Laboratory of Applied Pharmacokinetics
USC School of Medicine
Consultant in Infectious Diseases,
Children’s Hospital of Los Angeles
4650 Sunset Blvd, MS 51
Los Angeles CA 90027
|
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@lists.ucdenver.edu with "PK calculation when the drug itself is the endogenous substance" as the subject |
Copyright 1995-2014 David W. A. Bourne (david@boomer.org)