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I work in a multidisciplinary ICU and I was wondering if anyone has heard
of software to aid management of aminoglycoside dosing and dose interval in
critically ill patients...taking into account their level of renal
dysfunction etc. We normally use a once-daily dose regime adjusted
according to trough levels. Also is anyone aware of specific data on the
pharmacokinetics of gentamicin in this patient population (ie sepsis etc)
Dr. A. Ferguson
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> Reply-to: PharmPK.-at-.pharm.cpb.uokhsc.edu
> Date: Fri, 7 Nov 1997 11:27:50 -0600
> From: "andrew.ferguson"(by way of
>David_Bourne)
> To: Multiple recipients of PharmPK - Sent by
>
> Subject: Re: Aminoglycoside dosing in critical care
> PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
> I work in a multidisciplinary ICU and I was wondering if anyone has heard
> of software to aid management of aminoglycoside dosing and dose interval in
> critically ill patients...taking into account their level of renal
> dysfunction etc. We normally use a once-daily dose regime adjusted
> according to trough levels. Also is anyone aware of specific data on the
> pharmacokinetics of gentamicin in this patient population (ie sepsis etc)
>
You may consider trying Adapt II or USC Pak software. The former
will require more programing experience. There is a website of Adapt
II (Biomedical Simulations Resource - Univ of CA - LA).
Information about USC Pak can be obtained from Roger Jellife. There
are other programs with less versitability such as the Abbott
Program, but I have not used this. If you plan to use a program for
dosing - one capable of Bayesian estimation would be best. With
Bayesian estimation, obtain serum concentrations about 1.5 to 2.5
times the expected half-life.
Trough levels are not the best for once daily dosing. If dosed
correctly, the aminoglycoside concentration should be not-detectable
at the trough.
> Dr. A. Ferguson
>
> Also see: http://www.cpb.uokhsc.edu/pkin/pkin.html
>
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Reply-to: PharmPK.-a-.pharm.cpb.uokhsc.edu
Date: Fri, 7 Nov 1997 11:27:50 -0600
From: "andrew.ferguson"(by way of
David_Bourne)
To: Multiple recipients of PharmPK - Sent by
Subject: Re: Aminoglycoside dosing in critical care
PharmPK - Discussions about Pharmacokinetics
Pharmacodynamics and related topics
I work in a multidisciplinary ICU and I was wondering if anyone has heard
of software to aid management of aminoglycoside dosing and dose interval in
critically ill patients...taking into account their level of renal
dysfunction etc. We normally use a once-daily dose regime adjusted
according to trough levels. Also is anyone aware of specific data on the
pharmacokinetics of gentamicin in this patient population (ie sepsis etc)
Dr. A. Ferguson
As to your question about software for PK monitoring of
aminoglycosides, I would suggest 'MW\Pharm' (Mediware, Groningen, the
Netherlands, contact A. Vinks Ph.D., Apotheek Haagse Ziekenhuizen,
2504 AC Den Haag, The Netherlands tel +31 70 321 7217)
This software also comes with population subsets of
several aminoglycosides developped in several (academic) hospitals in
our country
Regards,
Mees Vervelde, PharmD
With kind regards,
M.L. Vervelde, Pharm.D.
University Hospital Utrecht
phone : +30 250 7218
fax : +30 251 6765
e-mail: m.vervelde.aaa.apoth.azu.nl
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Hello!
About Aminoglycoside dosage at ICU.
I just wanted to tell you that MW Pharm has given us a lot of trouble at
our TDM unit.
We have tried to contact the manufacturer several times - without luck. I
have asked for for references about who have used this sofwtware, proof of
validation etc.
I would try to contact ClydeSoft at The Western Infirmery at University of
Glasgow. They produce an excellent baeysian program called OPT (Dr. Andrer
Kelman, e-mail: Andrew.kelman.at.clinmed.gla.ac.uk)
Sincerely,
Thomas Senderovitz, M.D.
Unit of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen
Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark
E-mail: t.senderovitz.aaa.vip.cybercity.dk
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As manufacturer of MW\PHARM I strongly object against the message of mr.
Senderovitz.
Mr. Senderovitz did succesfully contact us by telephone and by fax d.d.
October 30 asking reference- and validation information. Nor in this fax,
nor later on he informed us about the kind of problems he had experienced
with MW\PHARM. In order to answer him in the best possible way, we have
been busy in preparing the desired information for him. Instead of
informing about our progress, he immediately uttered his grief into the
public discussion.
..
Fortunately, we feel strongly supported by our > 250 professional MW\PHARM
users in >14 countries who are using MW\PHARM in Clinical Pharmaceutical
settings, Schools of Pharmacy and Pharmaceutical Industries. In the
Netherlands MW\PHARM has been declared as the standard program to be used
by the Hospital Pharmacists and it was chosen in Germany as "best program"
for TDM purposes.
If you want to evaluate the quality and usefulness of MW\PHARM for
yourself,
please contact us at: 101465.3266.-a-.compuserve.com
and ask for free information material, demo-version or user-references.
Eddy van Essen
MediWare BV
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Dear Dr. Ferguson:
There are several software packages that are designed to be helpful in
aminoglycoside dosing in critically ill patients. The Abbottbase one is
good, and also the MW/Pharm software from Groningen, the Netherlands, and
OPT, from Glasgow. Our own USC*PACK software has been around for the
longest of any software package I know, and is specifically designed to
model the behavior of AG's and other drugs so that the pk model of the drug
can keep up with rapid changes in a patient's renal function from dose to
dose, for example, and also with changing body weight from dose to dose.
CCr can be computed from a pair of serum creatinine samples and age,
gender, height, and weight, so that serum creatinine can be changing widely
from sample to sample, and the model can keep up with these changes.
There are population AG models for general medical patients, ICU
patients,
otherwise healthy young patients (teens and early 20's), those with spinal
cord injuries, and newborns. You can also enter and store any other PK pop
model for any drug you wish, as long as it has an absorptive, a central,
and (if needed) a peripheral compartment. Elimination can be specifically
expressed as an increment of Kel per unit of CCr, with a nonrenal intercept.
These PK models use Bayesian approaches to make individual,
patient-specific PK models. These can also be linked to models of diffusion
into porous spherical objects such as endocardial vegetations of a stated
diameter, using diffusion coefficients obtained from animal studies, to
compute possible drug concentrations in its various layers, and in the
center of such a vegetation, and also to simulate the contribution of the
post-antibiotic effect.
The PK and the diffusion models can also be linked to models of
bacterial
growth and kill which can be used to evaluate the ability of a certain
regimen to kill well or not under defined circumstances. These Zhi models,
developed with Drs. Pascal Maire and Xavier Barbaut, use data of the rate
constant for growth in the logarithmic phase and the most rapid kill rate
found with in vitro studies. This can be combined with data of each
patient's known or estimated MIC to then model the possible growth and kill
of organisms under such defined circumstances, to better understand the
ability of various regimens and serum concentration profiles to be
effective or not.
Hope this helps.
Sincerely,
Roger Jelliffe
At 11:27 AM 11/7/97 -0600, you wrote:
>PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
>I work in a multidisciplinary ICU and I was wondering if anyone has heard
>of software to aid management of aminoglycoside dosing and dose interval in
>critically ill patients...taking into account their level of renal
>dysfunction etc. We normally use a once-daily dose regime adjusted
>according to trough levels. Also is anyone aware of specific data on the
>pharmacokinetics of gentamicin in this patient population (ie sepsis etc)
>
>Dr. A. Ferguson
>
>Also see: http://www.cpb.uokhsc.edu/pkin/pkin.html
>
************************************************
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
new software and upcoming workshops and events!!
It is http://www.usc.edu/hsc/lab_apk/
************************************************
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Dear Dr Ferguson
In terms of software for dose individualisation of Ags and indeed many
other drugs there are a number of programs available. A review by
Buffington et al (Clin Pharmacokinet 1993; 25:205-216) specifically
discusses this issue. In essence Bayesian methodology seems to be widely
used and appears to be very useful. To my knowledge all programs that use
Bayesian methods use the maximum *a posteriori* (MAP) objective function,
originally described by Sheiner et al (Clin Pharmacol Ther
1979;26:294-305). Minimisation of this objective function will locate the
mode values of the parameters. Therefore any computer program that uses
the MAP objective function and uses an accepted method of minimisation of
this function, eg simplex, Marquardt Levenberg (etc) will essentially yield
*identical* results. A good program will also allow you to input your own
prior model for a new or existing drug (which would be useful for your own
patient group).
In summary therefore it shouldn't matter which software you choose that
meet this criteria, and therefore choice should be based on cost,
availability and backup service.
> Also is anyone aware of specific data on the
> pharmacokinetics of gentamicin in this patient population (ie sepsis etc)
There are some publications on this already. A useful initial reference is
given by: Dager (Ann Pharmacother 1994;28:944-951).
I hope this helps.
Regards
Steve Duffull
=======================Steve Duffull
Christchurch
New Zealand
Ph +64 3 3815280
Fax +64 3 3640902
Email sduffull.-at-.clear.net.nz
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