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Dear Members
There is a little debate over confident terminal t1/2 values in non-
compartmental analysis. Let's say we have a PK data for 24 hr blood
collection interval. After non-compartmental analysis, we get the
estimated t1/2 values as 30 hr. In this case, is a 30 hr for t1/2
reliable considering we only have 24 hr data? If not, how can we set
a reliable range of t1/2 values? There are a couple of opinions on
that. First, blood collection interval is the maximum reliable t1/2.
For instance, for 24 hr blood collection interval, t1/2 values will
not be reliable over 24 hr. Second, half of the blood collection
interval is the maximum reliable t1/2. The logic of this argument is
that we should be confident to see terminal phase after at least 50%
of drug is eliminated. In the same example, 12 hr will be maximum
reliable t1/2. Third opinion is to consider the time interval to be
used in determining terminal phase. Let's say we have a PK data for
24 hr blood collection interval. In non-compartmental analysis,
terminal t1/2 was estimated using last three data point, i.e., 12 hr,
16hr, 24 hr postdose. The interval for terminal t1/2 selection is 12
hr (24 hr - 12 hr). In this case, reliable t1/2 will be 6 hr maximally.
Thanks
Sun Ku Lee, Ph.D.
Staff Scientist, Pharmacokineticist
Pharmacokinetics and Pharmacodynamics
Covance Laboratories
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The following message was posted to: PharmPK
Dear Sun,
To accurately estimate a half-life, you should sample out to at least 4
times the half-life into the terminal elimination phase. So a half-life
of 24 h requires 96 h of sampling, corresponding to 93.75% excreted.
Half-lives determined with sampling periods less than 4 times the
half-life are not without value, but are less reliable, and you run the
risk of missing a more slow phase of the elimination that only shows up
late in the curve. Later on in the development of a drug, when more
sensitive assays are developed, and samples are taken for longer times,
these slower phases are then discovered.
Jan
--
Jan Hendrik Beumer
Pharm.D., Ph.D.
Assistant Professor of Pharmaceutical Sciences
School of Pharmacy
The Hillman Cancer Center
Research Pavilion, Suite G.27d
5117 Centre Avenue
Pittsburgh, PA 15213-1863
Email: beumerjh.at.upmc.edu
http://www.pharmacy.pitt.edu/Directory/dir.lasso?Last=BeumerJ
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