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Dear friends:
I have looked up about which is important clinically, the pre (trough)
or the post (peak) vancomycin level to determine the efficacy and
toxicity of vancomycin. I only found two review article talking about
this subject recommending to use only the trough (pre) level to determine
the efficacy and toxicity of vancomycin since it does not have the
characteristic of "concentration dependent killing" as the
aminoglycosides. So what is your experience and thought. Thank you
Dr/ Mohammed AL-Toukhi, Pharm.D
Clinical Pharmacist
E.mail---al-toukhi.aaa.juno.com
Home Page--http://www.angelfire.com/mo/mzsr/indexe.html
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There are several published nomograms or dosing methods for
vancomycin in the literature. The Moellering nomogram is probably
the most widely used (Moellering RC, et al. Ann Intern Med
1981;94:343-6.). Also see Matzke GR, et al. Clin Pharm 1985;4:311-5.
These methods are based on achieving a mean steady state
concentration of 15 mg/L. It is true that killing of susceptible
bacteria by vancomycin is similar to beta-lactams - more time
dependent than concentration dependent. Thus the goal is the
maximize the time that concentrations remain above a certain
concentration. It is not important to achieve a high peak
concentration. A typical MIC for vancomycin is 1-2 mg/L. Thus with
usual dosing strategies, the concentration is above the MIC for 100%
of the time.
There are no good studies that percisely define the
pharmacodynamic targets for vancomycin. We know that many of the
organisms that are treated are tolerant to vancomycin. That is the
MBC is considerably greater than the MIC for vancomycin. In terms
of trough concentrations we do not know what the optimal Ctrough:MIC
ratio should be. Until better studies are performed, the target of a
mean steady state concentraiton of ~15 mg/L is reasonable. Having
trough concentrations > MIC is also reasonable. Many hospitals have
defined desired trough concentrations (e.g. 5-10 mg/L), however,
this target is not based on good studies.
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Dear Mohammed:
I think in general that you are right. Vanco is a
non-concentration-dependent drug, and so the useful thing seems to be to
have the trough be several times the MIC, and then things should be OK.
George Drusano tells me he likes a trough of about 10ug/ml, which is about
5 times the MIC if the usual MIC is 1.0, and one allows for 50% binding to
proteins. This all seems good to me.
However, when one monitors trough levels to see if they are
efficacious,and if there is any problem, then you usually need at least the
basic pair of levels (peak and trough, or a D-optimal version of that, in
order to make the correct dosage adjustment, and to know the relative
contribution of Vd and Kel to the clearance, which is made up of these 2
parameters, although many will say it is the other way around, and we can
talk about that). In addision, it may well be useful to get another third
level about 2.5 hrs after the end of the IV infusion, to perceive the
exchange rate constants well between central and peripheral compartments.
Sander Vinks in the Hague has done D-optimal designs for Vancomycin. He
could also be helpful here. If you only measure the trough you only really
know the clearance, and you may want to know more of the structure that this.
Another small thing. One does not monitor levels to correcate the peak
with efficacy (or something like that) or the trough with toxicity (or
something like that). You monitor levels to make an individualized model of
the behavior of the drug in that individual patient, and to compare the
behavior of the model with the clinical behavior of the patient. Only then
can you really evaluate the patient's sensitivity to the drug, and only
then can you decide whether or not the initial target goal was correctly
chosen or not, and only then can you do a good job of deciding what other
target (if needed) to choose. Then, one wants to design the regimen to hit
the target goal with the greatest precision.
Does this help? Let's talk. All the best,
Roger Jelliffe
************************************************
Roger W. Jelliffe, M.D.
USC Lab of Applied Pharmacokinetics
CSC 134-B, 2250 Alcazar St, Los Angeles CA 90033
Phone (213)342-1300, Fax (213)342-1302
email=jelliffe.-a-.hsc.usc.edu
************************************************
Take a look at our Web page for announcements of
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It is http://www.usc.edu/hsc/lab_apk/
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Dear Mohammed,
The importance of monitoring for vancomycin toxicity has diminished somewhat
over the past few years. Studies in the literature have not demonstrated a
definite link between toxicity & the level of vancomycin whether peak or
trough. The trough level is important in order that adequate levels are
obtained over the MIC of the bacteria. Vancomycin does not demonstrate
concentration dependent killing that is, a higher dose does not produce a
better effect. For the younger patient, all that is probably necessary is a
trough level. For the older patient, a peak & trough maybe obtained in order
to calculate possible dosage adjustments.
Regards
Gail Neilson,
Senior Pharmacist,
Alternative Site Infusion Service,
Princess Alexandra Hospital,
Ipswich rd,
Woolloongabba, Queensland,
Australia, 4102.
Ph 61 07 32407039 or Mobile 041 2365 294
Email: G.Neilson.-a-.mailbox.uq.edu.au
Research Masters student in Home Parenteral Programs,
School of Pharmacy,
University of Queensland,
St.Lucia,
Queesland, Australia.
Secretary & Editor,
Australian Home and Outpatient Intravenous Therapy Association,
c- Dept. of Infectious Diseases,
Monash Medical Centre,
Melbourne, Australia.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)