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Dear Friends,
I would like to do the population pharmacokinetic characterisation of
gentamicin. Studies found in the literature have used different time
samples for the same. How ever, all these have been from the
retrospective collection of data from the patients. Since it is not
a practice at our hospital, like most Indian hospitals, to monitor
drug level of gentamicin, I have to do a prospective study. Kindly
let me know the minimum number of samples to be taken from each
patient with the time intervals in once daily and twice daily dosing
regimen.
Thanks a lot.
Regards
Rajendiran
Government Head Quarters Hospital,
Udhagamandalam 643 001
South India.
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"S.D.Rajendran (by way of David Bourne)" wrote:
> I would like to do the population pharmacokinetic characterisation of
> gentamicin. Studies found in the literature have used different time
> samples for the same. How ever, all these have been from the
> retrospective collection of data from the patients. Since it is not
> a practice at our hospital, like most Indian hospitals, to monitor
> drug level of gentamicin, I have to do a prospective study. Kindly
> let me know the minimum number of samples to be taken from each
> patient with the time intervals in once daily and twice daily dosing
> regimen.
If it is not your practice to use PK as part of clinical care to
improve dose individualization I wonder why you are doing this kind
of study? If you explained your objectives more clearly e.g. you wish
to see if eating curry affects the volume of distribution, then it
might be possible to give you some more specific advice.
--
Nick Holford, Divn Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:n.holford.aaa.auckland.ac.nz
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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Dear Raj,
I would suggest a minimum of two blood samples to be
able to construct a pop PK for gentamicin especially
if there is difficulty to obtain more blood samples
from each patient. With once daily use of gentamicin,
one sample following parentral administration and the
other after 6-8 hours are suitable. In case of twice
daily administration of the drug, peak and trough
levels can be used.
regards,
Ehab EL Desoky,
Pharmacology Dept
Faculty of medicine
Assiut univ. Egypt
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Dear Dr. Rajendran:
The usual peak and trough strategies for TDM are often too sparse
for anything except a 1 compartment model. Yet gentamicin clearly has a
peripheral compartment, which may well be related to the clinical response
of patients with infections that are not primarily septic or bacteremic. It
would be most useful to develop a protocol that stands a chance of getting
you a good 2 compartment model.
It is difficult to avoid the issues of experimental design, and a
good rule of thumb is to have at least one serum sample for each parameter
you would like your model to have. With a peripheral compartment, that is
at least 4 parameters, and thus 4 samples.
Do not freeze these into 4 fixed times. Spread them around at
various time points in the dose interval. You will need to examine the
behavior of the drug at as many different points during the dose interval
as possible. D-optimal strategies are often useful guides. But do not fix
these times. move them around to somewhat different times with each new
cluster of about 4 samples that you get with each patient, so that in the
end, you have data at many different times after the dose, to best capture
the dynamic behavior of the drug. Don't forget Jerry Shentag's 2
compartment model of gentamicin.
In general, also, I believe that we usually do not get enough
samples during routine TDM, and we call that "being practical". However,
when we do this, we can learn only very little from this time, money, and
work. We are not investing this effort in each patient to get more
information. I believe this is a waste of money, and that with a few more
samples, well chosen, we can learn a great deal more about the behavior of
drugs in patients. Models also have important peripheral compartments, and
we learn essentially nothing about all this from most TDM stragegies.
I look forward to hearing from you further,
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D. Professor of Medicine,
Division of Geriatric Medicine,
Laboratory of Applied Pharmacokinetics,
USC Keck School of Medicine
2250 Alcazar St, Los Angeles CA 90033, USA
email= jelliffe.-a-.usc.edu
Our web site= http://www.lapk.org
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Dear Jelliffe,
I agree with you that availability of more blood
samples gives better chance for modeling and PK
estimation. However, in practice, more blood sampling
is sometimes difficult e.g,in marasmic and
malnourished pediatric patients who have severe chest
infection and need gentamicin as an antimicrobial
agent.
What is your opinion if one can suggest 3 blood
samples distributed as follows: one sample immediately
following drug administration, a second one near the
end of dose interval, and a third (middle) one
randomly taken (i.e. not at a fixed time) within the
dose interval.
regards,
Ehab EL Desoky
Pharmacology Dept
Faculty of Medicine
Assiut Univ. Egypt
[If that 'end of interval' point is too far down the exponential time
curve it may not give you very much information. Assay error or being
to far from optimal sample times may make it a poor choice. It may be
convenient but it isn't as useful as a sample collected closer to 1/k
(for one compartment models) or other times as suggested by optimal
sampling - db]
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Dear Dr. El Desoky:
Thanks for your note. I wince at the words "in practice". That is
the problem. Usual practice does not take into account, usually, the basic
issues of optimal experimental design, and it should. That is my point. I
think we need to get mote data points, and to place these points where the
data will contain the most information.
I think your suggestion is generally a good one. A sample
immediately after infusion usually is most informative with respect to the
volume of distribution. You are right that a trough often (especially with
once daily dosing!) is too low to be most informative. Often a sample when
the concentrations are about 1/3 of the peak is informative - like the 8
hour sample many have suggested when renal function is reasonable. I agree
that another sample, taken at various times after the dose is useful to
help us understand the exchanges between serum and a peripheral
compartment, and that is what I think we need to understand better.
For the present, the basic principles of D-optimal, or some
similar method of optimal design is useful to use in planning these optimal
times, and should be much more used in practical methods of TDM clinically.
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D. Professor of Medicine,
Division of Geriatric Medicine,
Laboratory of Applied Pharmacokinetics,
USC Keck School of Medicine
2250 Alcazar St, Los Angeles CA 90033, USA
email= jelliffe.-at-.usc.edu
Our web site= http://www.lapk.org
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)