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Dear all,
During the past few weeks, several questions have been submitted to
the list with regard to antibiotics PK and PD. All mails discuss AUC
or AUC above MIC or similar estimates and their supposed correlation
with therapeutic outcome.
I might sound naive, but could anybody explain to me why there are no
mechanistic PK/PD models in widespread use when it comes to
antibiotic therapy, despite several elegant works already published?
Why are we still using AUC or Cmax or variations of these parameters
when it comes to antibiotics? Most other PK/PD models are
successfully modeled using more or less mechanistic approaches so
what is so special about antibiotics that requires using this rather
(in my opinion) primitive approach?
Toufigh Gordi
Associate Director of Clinical Pharmacology
CV Therapeutics Inc.
3172 Porter Dr.
Palo Alto, CA 94304
Tel.: 650-384-8929
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The following message was posted to: PharmPK
Hi Toufigh,
Thanks for pointing out the feasibility and need for more mechanistic
PK/PD
models for antibiotics. Actually, there do exist :-)
For example, Dr. Hartmut Derendorf's group at University of Florida
has done
a lot of work on that (Bacteria kill curves and models). You can try
search
on pubmed by key words: Derendorf & antibiotics.
Best wishes,
Qi
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The following message was posted to: PharmPK
Toufigh,
I absolutely agree with you, and our group is doing mechanistic
modeling for
just the reasons you state. However, there are a few reasons why the
'simpler' simpler approach for antibacterials continues to be used. The
biggest point is that a) the simple approach works pretty well, and
is easy
to implement...you don't need to be a kineticist or a modeler to do
it. It
is also very difficult to get some of the data that would be useful
for more
sophisticated approaches, such as a quantitative measure of the
number of
bacteria present in an infected patient. The mathematical
consideration of
host immune factors, site of infection concentrations, and presence or
emergence of resistance subpopulations, etc. makes the typical
clinician's
eyes glaze over. Not to mention the drool that goes along with it.
Patrick smith
Buffalo, ny
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