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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.
Sun Ku Lee, Ph.D.
Staff Scientist, Pharmacokineticist
Pharmacokinetics and Pharmacodynamics
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The following message was posted to: PharmPK
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 Hendrik Beumer
Assistant Professor of Pharmaceutical Sciences
School of Pharmacy
The Hillman Cancer Center
Research Pavilion, Suite G.27d
5117 Centre Avenue
Pittsburgh, PA 15213-1863
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