Back to the Top
Dear readers,
For a drug which exhibits plasma concentration-time data fitting best with two
compartment models, a beta half-life of 4 hrs was estimated. How many beta
half-lives should the blood sampling continue? Is there any significance to
alpha half-life (which was only 8-10 minutes in this case)as far as sampling
is concerned?
Thanks for any suggestions.
Back to the Top
Hi
Beta half-lives should typically extend over 3-4 half-lives.
For alpha half-live, you should try and obtain 3 points during the half-life
to adequately estimate the alpha.
Jeffrey L. Larson, Ph.D.
Director of Toxicology and Pharmacokinetics
Tanox, Inc.
4888 Loop Central Drive
Houston, TX 77081-2225
(713) 578-4212
Note: Any use, dissemination, forwarding, printing or copying of this e-mail
without consent of Tanox, Inc. is not authorized. Further, this
communication may contain confidential information intended only for the
person to whom it is addressed, and any use, dissemination, forwarding,
printing or copying of such confidential information without the express
consent of Tanox or in violation of any agreements to which the recipient is
subject is prohibited. If you have received this e-mail in error, please
immediately notify the sender and delete the original and all copies. Any
views or opinions expressed may be solely those of the author and do not
necessarily represent the views or opinions of Tanox, Inc.
Back to the Top
Hi Dr. Larson,
Thank you for the information in your email.
I am still not clear about the optimal sampling times and would greatly
appreciate your suggestions in that regard:
My compound's iv/oral profile shows a very rapid initial drop, such that at 2
hrs, there is only very little (a little over the limit of
quantitation)showing.
As a result I had discontinued sampling after 3 hours. The Winnonlin
program's 2-compartment model provides an estimated beta half-life of 6 hours
or so. Does you suggestion about the half-life imply that I should have
sampled for much longer than the 3 hours I had originally done?
Thank you.
Panteha
Back to the Top
Dear Pharmacokinetist,
one common procedure of blood sampling is this rule:
The blood sampling period should be continued for at least
three-times, preferably five-times, the terminal half-life following
tmax. Such a procedure is only meaningful if the bioanalytical
methodology has been correspondingly developed i.e. following
administration of a certain single dose, the mean plasma
concentration of the compound of interest [drug and/or metabolite(s)]
at time t = 5-t1/2 should be greater than the lower limit of
quantification (LOQ).
The time points for blood sampling are usually fixed as follows: the
total number of time points is ideally 15. The first five time points
are selected before tmax (inclusive), the second five time points
between tmax and t1/2 (inclusive) and the last five time points
between t1/2 and five-times t1/2 (inclusive). If the study procedures
are restricted to 12 time points for blood sampling, four instead of
five time points should be selected within each of the aforementioned
three periods.
This procedure is appropriate to characterize the PK profile of the
data you mentioned, too (using the cut point between alpha and beta
phase instead of tmax).
For more details see my textbook 'Parameters for Compartment-free
Pharmacokinetics, Standardisation of Study Design, Data Analysis and
Reporting'.
Best Regards,
Willi Cawello
Willi Cawello, PhD
Senoir Scientist Pharmacokinetics
SCHWARZ BIOSCIENCES GmbH
Alfred Nobel Str. 10
D40789 Monheim am Rhein, Germany
willi.cawello.-at-.schwarzbiosciences.com
+02173 481480
Back to the Top
Dear Willi and others:
Your approach to blood sampling times is interesting and makes
good common sense. There are also ways to optimize the information
contained in the data by computing the D-optimal times for example, based
on your current parameter estimates in the model you think is relevant. A
good reference is D'Argenio D: Optimal Sampling Times for Pharmacokinetic
Experiments, J. Pharmacokin. Biopharmaceut. 9: 739-755, 1981. There are
also a number of other similar optimality criteria to consider.
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D. Professor of Medicine,
Laboratory of Applied Pharmacokinetics,
USC Keck School of Medicine
2250 Alcazar St, Los Angeles CA 90033, USA
email= jelliffe.at.hsc.usc.edu
Our web site= http://www.lapk.org
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)