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The following message was posted to: PharmPK
I would like to know the definition for Tlag (a lag time). How is the
Tlag calculated? Is Tlag only for compartment models, not
non-compartment model?
I appreciate your help!
Chunqin Deng, PhD
Senior Biostatistician
PPD Development
(919) 462-5173
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The following message was posted to: PharmPK
Hello,
Tlag is an empirical parameter, that signifies the delay between the
time
of dosing and time of appearance of concentration in the sampling
compartment. Typically, Tlag is used to characterize the delay in
absorption
of orally given drugs (e.g.:due to slow dissolution). This parameter is
best
estimated using a compartment model.
Eye-balling is probably the only non-modeling approach.
Regards,
Joga Gobburu
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The lag-time can be estimated in compartmental models and also by
non-compartmental procedures. An example of the latter is in J. Pharm.
Sci. 87, 608-612, 1998 ("Model-independent estimation of lag-times with
first-order absorption and disposition").
Laszlo Endrenyi, Ph.D.
University of Toronto
Department of Pharmacology
Toronto, Ont. M5S 1A8
Tel: (416) 978-8620
Fax: (416) 978-6395
e-mail: l.endrenyi.at.utoronto.ca
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If would like to get some basics covered on this topic, I would
recommend you to read a book chapter titled Diffusion and Dissolution in
Physical Pharmacy text book by Alfred Martin et al.
Azher M. Hussain, Ph.D
Post Doctoral Researcher
P450 Inhibition
Xenotech, LLC
Phone: 913 227 7172
Email: ahussain.aaa.xenotechllc.com
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The following message was posted to: PharmPK
If a process that develops in the body over a course of time, such as
drug absorption, drug dissolution, drug bioavailability, etc. is
delayed,
Tlag, or in other words a time delay, is an important parameter of this
process.
This parameter is not dependent on a method used to study a particular
process, as pointed out by Prof. Endrenyi.
In general, a process that develops in the body over a course of time
can exhibit more than one time delay as exemplified e.g. in studies:
Durisová M, Dedík L, Balan M. Building a structured model of a complex
pharmacokinetic
system with time delays. Bull Math Biol 1995; 57: 787-808,
Dedík L, Durisová M, et al. Model of lymphocyte migration
in merino ewe under physiological conditions. Physiol Res 1999; 48:
525-8,
Copies of these studies can be found in the directory HELP of the
software
package
CTDB, a version of which is available at
http://www.uef.sav.sk/advanced.htm
Regards,
Maria Durisova, PhD, DSc,
Head of Department of Pharmacokinetics
and Scientific Secretary
Institute of Experimental Pharmacology
Slovak Academy of Sciences
841 04 Bratislava 4
Slovak Republic
Phone/Fax: +421 2 54775928
http://www.uef.sav.sk/durisova.htm
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The following message was posted to: PharmPK
Dr. Deng and all:
Another non-compartmental approach to the estimation of Tlag was
described by Saunders and Natunen in 1973. In this approach, the first
few (3-4) absorption time points are fit to a second degree polynomial
equation, i.e. C = a + bt + ct^2, extrapolated to zero. Using this
method, the fitted curve initially dips below X (negative Y) and then
crosses X at C=0, t= t-lag on ascent and fit through the absorption
data points. This method is non-compartmental despite the title of the
paper. However, I would agree with that proposed by the others, of
using more modern (T > 1973) compartmental or other non-compartmental
approaches which allow determination of the full range of PK parameters
you probably seek.
Ref: Saunders L, Natunen T. A stable method for calculating oral drug
absorption rate constants with two compartment disposition. J Pharm
Pharmac 25 (suppl): 44p-51p, 1973.
Bert Lum
Stanford University
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)