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I just wonder how other clinicians adjust Vancomycin
levels based on a trough level only. We are targeting 15-20 mcg/ml
for MRSA pneumonia and our physicians prefer this narrow range not
above or below this target. I frequently estimate my Cmax assuming a
Vd=0.7L/kg and use this value with the patient specific level to
calculate my kinetic parameters for Vancomycin and subsequently
estimate the new dosage regimen to achieve my target troughs. The
traditional method of just increasing or decreasing the frequency of
the dose seems to overshoot or undershoot the target.
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Bayesian computer programs are perfect for this type of dosing. With
just a trough level (not even at s-s!) You'll get a complete kinetic
workup, plus be able to compute the necessary dose and dosage
interval. If your docs want that tight of dosing, there is no way
you'll be able to get it by using 1000 mg q __ h.
--Larry Bauer
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I will use a Vd approximation (ie. 0.9L/kg) as well, in the absence of
peak data, to estimate Ke and then design a dosing regimen around
that,
for targeted trough concentrations. For most critically ill patients,
however, I will order a peak (1 - 2 hours post) and a trough for all
initial regimens; in order to better identify the parameters. After
this, I will just order trough levels in my patient.
Robert Ariano, PharmD, BCPS, FCCM
Clinical Pharmacist Critical Care
St.Boniface General Hospital; &
Associate Professor of Pharmacy,
& Medicine, University of Manitoba,
204-237-2050 Phone
204-235-1476 FAX
rariano.-a-.sbgh.mb.ca
www.sbgh.mb.ca
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Check out "Basic Clinical Pharmacokinetics", by Michael E.Winter
There is a great chapter on Vanco. (I have the 4th edition, 2004)
Good luck!
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Larry,
You wrote (labauer.-at-.u.washington.edu):
> Bayesian computer programs are perfect for this type of dosing. With
> just a trough level (not even at s-s!) You'll get a complete kinetic
> workup, plus be able to compute the necessary dose and dosage
> interval. If your docs want that tight of dosing, there is no way
> you'll be able to get it by using 1000 mg q __ h.
I fully agree that Bayesian forecasting is the best algorithm to
apply for target concentration intervention with vancomycin (or any
other drug that might benefit). This part of the technology is well
established and the science clearly understood e.g. early work:
Schumacher & Barr 1984, Vozeh et al. 1985; vancomycin: Polard et al.
1999, Wrishko et al. 2000 ; integrated methods: Lenert et al. 1992
But whatever approach is used to calculate the dose it seems to me
that the blind are leading the blind. What is the target
concentration or concentration profile? Is it peak, trough, or
average (equivalent to AUC)? Or a combination of concentrations? If
you choose to reply then please support your proposals with
references to the published original literature and look carefully at
how well the target is supported by the outcome data. Please don't
propagate anecdote and urban myths from textbooks and uncritical
reviews and 'what we do here is...".
Assuming you have a good idea of a target concentration then what is
the safe and effective variability (SEV) around that target that
would give acceptable clinical outcome? In Larry's words "If your
docs want that tight a dosing" - just what does "tight" mean in exact
terms? An example of SEV would be defined by 90% of patients within
20% of the target (Holford 1999).
If you know the SEV and understand the predictable factors (e.g.
size, renal function) that influence the PK parameters then it is
possible to know just how close one can get to achieving individual
patient concentration variation to the desired SEV. This can be used
to identify if target concentration intervention is unnecessary (size
and renal function might be enough) or useless (day to day
variability in individual PK may be too big to make predictions from
measured concs) (Matthews et al 2004).
Nick
Schumacher GE, Barr JT. Bayesian approaches in pharmacokinetic
decision making. Clin Pharm. 1984 Sep-Oct;3(5):525-30.
Holford NHG. Target Concentration Intervention: Beyond Y2K. Br J Clin
Pharmacol. 1999;48:9-13.
Lenert LA, Lurie J, Sheiner LB, Coleman R, Klostermann H, Blaschke
TF. Advanced computer programs for drug dosing that combine
pharmacokinetic and symbolic modeling of patients. Computers &
Biomedical Research. 1992; 25(1):29-42.
Matthews I, Kirkpatrick C, Holford NHG. Quantitative justification
for target concentration intervention - Parameter variability and
predictive performance using population pharmacokinetic models for
aminoglycosides. British Journal of Clinical Pharmacology. 2004;58
(1):8-19.
Polard E, Le Bouquin V, Le Corre P, Kerebel C, Trout H, Feuillu A, et
al. Non steady state and steady state PKS Bayesian forecasting and
vancomycin pharmacokinetics in ICU adult patients. Ther Drug Monit.
1999 Aug;21(4):395-403.
Vozeh S, Hillman R, Wandell M, Ludden T, Sheiner L. Computer-assisted
drug assay interpretation based on Bayesian estimation of individual
pharmacokinetics: application to lidocaine. Ther Drug Monit. 1985;7
(1):66-73.
Wrishko RE, Levine M, Khoo D, Abbott P, Hamilton D. Vancomycin
pharmacokinetics and Bayesian estimation in pediatric patients. Ther
Drug Monit. 2000 Oct;22(5):522-31.
--
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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Hi- I find it really interesting in this day and age that folks are
using estimated parameters (like Vd) to "calculate" a k for a patient
that may or may not be even close to the real elimination rate
constant. Of course, all of these errors accumulate to produce a
dose for the patient that is not optimal.
Jelliffe and Sheiner and Beal (and others) did all the ground work
and validation on Bayesian computer programs in the '80s for gosh
sake! Some of these programs are available for free while others are
available for a nominal charge (for info, check out Dave's web
site). As TDM advances in the 21st century (trough-only monitoring
for vanco, extended-interval dosing for AGS, etc), these programs
will give individualized PK workups and the _best_ dose to achieve
desired steady-state concentrations. They are highly recommended
over the rough estimation techniques outlined in the first paragraph.
Larry Bauer, PharmD, FCP, FCCP
Professor
University of Washington
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