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The following message was posted to: PharmPK
Dear All,
I am a little bit confused of PK/PD parameter, AUC/MIC
(AUIC). Some sources (including the EMEA/CPMP
guidance) suggested using 24 hr AUC/MIC, however if
following the textbook on PK/PD correlation written by
Prof. Darendorf and Hochhaus, suggested 80% of 24
hr AUC should be above MIC (like AUC above MIC/MIC
not 24 hr AUC/MIC) . Can anyone give me any thought
or idea on using this parmeter? The number of 125
should be based on which AUC/MIC?? Moreover, it is
mentioned that AUC/MIC has no unit but it is
impossible, AUC (conc*time)/MIC(conc), thus the unit
should be time, isn' it? Thank you very much.
Korbtham Sathirakul Ph.D., M.B.A.
Department of Pharamcy, Faculty of Pharmacy
Mahidol University
Bangkok, Thailand
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The following message was posted to: PharmPK
> Moreover, it is
> mentioned that AUC/MIC has no unit but it is
> impossible, AUC (conc*time)/MIC(conc), thus the unit
> should be time, isn' it?
The AUC/MIC ratio is an empirical statistic conceived without any
discernible scientific theory. However, it might be rationalized by
defining the interval over which the AUC is observed. This is usually
the dosing interval. If the AUC is observed at steady state then AUC
divided by the dosing interval is the average steady state
concentration. The ratio of Css/MIC is dimensionless.
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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The following message was posted to: PharmPK
Dear Korbtham,
It is interesting to see that while mechanism-based models are getting
more attention in pharmacokinetics and pharmacodynamics in general,
most of the publications/research dealing with the antibiotics effects
continue to use AUC, AUIC, Cmax, AUC/24hrs,... to describe/predict
observed effect. I am not sure why the use of these parameters is so
persistent. However, mechanism-based models are being developed and
shown to be of value. The theoretical frame is available and several
papers (particularly in malaria but also other ) have been published.
Have you thought of such approach in modeling your data?
Toufigh Gordi, PhD
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I’m happy to see that the AUIC has found its way to this forum. I have
also wondered about the science behind this and Nick Holford (Thanks
again!) answered to this in a way that I can easily agree with.
As AUIC is the ratio AUC/MIC. This ratio is problematic, as already
mentioned, because of the unit. AUC is a robust entity but MIC is not.
MIC is determined generally in two-fold dilutions and is, therefore,
exponential. Any change in the MIC will at least double or halve the
AUIC. It is not uncommon that the variability in MIC determinations are
+/- 2 dilutions (without getting into the intra- or interlaboratory
variability). Therefore, I have hard time to understand the magical
AUIC value of 125 (whatever unit it is). I also think that volume of
distribution has a meaning in antimicrobial therapy. Now it looks like
it is inversely correlated to AUIC??
Stefan Soback
Kimron Veterinary Institute
Israel
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The following message was posted to: PharmPK
there are three different definitions for AUIC and it should not be
used for AUC/MIC ratio.
the unit for AUC/MIC ratio is time.
have look at the following paper :
Mouton J.W., Dudley M.N., Cars O., Derendorf H., Drusano G.L.
Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology
for anti-infective drugs
Int J Antimicrob Agents 2002;19:355-358.
johan mouton
Johan W Mouton, MD PhD
Dept Medical Microbiology and Infectious Diseases
Canisius Wilhelmina Hospital C-70
Weg door Jonkerbos 100
6532 sz Nijmegen
The Netherlands
tel + 31 24 3657514
fax + 31 24 3657516
email mouton.aaa.cwz.nl
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)