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Hello all!
I got such a wonderful response to my Chiou dilemma (thanks to all who
responded!) I thought I'd see if my luck is still holding. : )
1. Regarding vanco kinetics, our instructor gives the following equation:
Kel = 0.0044 + 0.00083(CrCl)
I can't find this in any of my kinetics resources, and it gives a very
different answer from the more commonly used Kel = ln(Cp1/Cp2)/time. So my
question is, is this a valid equation, and if so, is CrCl expressed in ml/min?
2. Is it necessary to wait 1.5 half-lives before drawing the first vanco
blood level?
3. If your vanco infusion is given over 2 hours instead of 1 hour, do you
still need to wait a full 3 hours to account for the distribution phase
before drawing a peak?
Thanks again in advance. I hope everyone had a most excellent Thanksgiving.
Cath
-----------------------------
Catherine Heyneman, Pharm.D. Phone: (208) 236-2743
ISU College of Pharmacy FAX: (208) 236-4305
Pocatello, ID 83209 E-Mail: cathy.aaa.elixir.isu.edu
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At 02:18 PM 12/3/96 -0600, you wrote:
>PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
>Hello all!
>
>I got such a wonderful response to my Chiou dilemma (thanks to all who
>responded!) I thought I'd see if my luck is still holding. : )
>
>1. Regarding vanco kinetics, our instructor gives the following equation:
>
>Kel = 0.0044 + 0.00083(CrCl)
>
>I can't find this in any of my kinetics resources, and it gives a very
>different answer from the more commonly used Kel = ln(Cp1/Cp2)/time. So my
>question is, is this a valid equation, and if so, is CrCl expressed in ml/min?
I expect CrCl is in ml/min here, i.e., a CrCl of 100 ml/min would yield Ke
of 0.0874, which probably gives you a half-life of about 8 hr.
>2. Is it necessary to wait 1.5 half-lives before drawing the first vanco
>blood level?
Define "first level"- first level after a loading dose? If so, probably not
(see later).
>3. If your vanco infusion is given over 2 hours instead of 1 hour, do you
>still need to wait a full 3 hours to account for the distribution phase
>before drawing a peak?
Why draw a peak any way? Vanco peaks have no real impact on outcome, and
are difficult to interpret due to the issues you are pointing out here. I'd
suggest either monitoring concentrations using troughs only (goal: 10-13
mg/L) or using a midpoint concentration (goal: 15-19 mg/L) to estimate AUC
and hence daily dose.
>Thanks again in advance. I hope everyone had a most excellent Thanksgiving.
>
>Cath
>
>-----------------------------
>Catherine Heyneman, Pharm.D. Phone: (208) 236-2743
>ISU College of Pharmacy FAX: (208) 236-4305
>Pocatello, ID 83209 E-Mail: cathy.-a-.elixir.isu.edu
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1. The equation Kel=0.0044 + 0.00083(ClCr) is derived from work done in the
late 70's and early 80's by Mollering using Bayesian modeling form POPULATION
kinetics of Healthy adults. Therefore, clinicians must evaluate the patient
in question prior to envoking a particular nomogram or equation to a specific
patient. An equation I use in clinical practice to estimate the inital
patient elimination rate constant is,
CL= (Vd) (Kel). This equation is more patient specific in that one integrates
the patient specific serum creatinine to calculate Cl. Many argements can be
posed such as aminoglycoside as well as glycopeptides clearence is not 100%
proportionate to creatinine clearence; however, the equation is more
individualized to the patient in question and allows for error on
conservative if clearence is high (note if serum creatinine is < 1 mg% use 1
) something the other equation does not do.
2. Vancomycin has been shown to distribute via more than one compartment
model ( Applied Phamracokinetics, 1992) and precise time for distribution has
not been clearly established; however, this poses no problem clinically
because definitive vancomycin peak levels have not been established and toxici
ty associated with 2hour post infusion (initiation) levels < 60mg/l have not b
een substantiated. The longer you wait the better, as the sole purpose of
drawing levels is to obtain patient specific pharmacokinetic parameters so
you can attain desired levels.
3. One should wait at least 1hour after adminstration to allow for
distribution of any givnen dose reguardless of infusoin time. Patients with
rapid clearence are will eliminate the drug if "peak" (because it really is
not a peak) is drawn too soon.
I hope this is helpfull to you and hope look forward to your evaluation of
the information! ;) !
Ruben Atencio R.Ph., B.C.N.S.P.
raUNMcop92 .at.aol.com
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1. Reference is Matzke GR, et al. Pharmacokinetics of vancomycin in
patients with various degrees of renal function. Antimicrobial Agents
and Chemotherapy. 1984;25:433-7.
Creatinine clearance is expressed as ml/min.
There are many reasons why a population prediction of k (and t1/2)
may not match calculations from actual patient values.
> Population predictors such as these are based on regression of k
vs CLcr in a number of patients. The are value is often not too high.
> Vancomycin concentration measurements often a problem if drawn
early after an infusion
> etc, etc, etc - see standard texts for such explanations
The equation is probably as "valid" as any other similar type
predictor taken from a sample of patients that may or may not be
reflective of the patient you are treating.
P.S. Population predictors for a number of drugs can be found in my
book (cheap advertising, eh)
Murphy JE (ed). Clinical Pharmacokinetics Pocket Reference. American
Society of Health-System Pharmacists, Inc., Bethesda, MD, 1993.
2. The usual recommendation is one to two HOURS (I assume this is
what you meant) after a one hour infusion in order to avoid
distribution phase when using one-compartment model approaches to
analysis. P.S., the equation above is for one-compartment
approaches.
3. The longer infusion time will mask more of the distribution
phase. However, many still recommend waiting the hour. As long as
you aren't using a short interval waiting the extra time should not
be a problem and may be a benefit in insuring the infusion is
actually completed.
Hope this helps.
John E. Murphy, Pharm.D.
Professor and Head
Department of Pharmacy Practice and Science
(520) 626-5730 (P), (520) 626-7355 (FAX)
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> Why draw a peak any way? Vanco peaks have no real impact on outcome, and
> are difficult to interpret due to the issues you are pointing out here. I'd
> suggest either monitoring concentrations using troughs only (goal: 10-13
> mg/L) or using a midpoint concentration (goal: 15-19 mg/L) to estimate AUC
> and hence daily dose.
I generally agree with the above but have a minor philosophical quibble.
IMHO the point of measuring one or more concs is to estimate clearance so
that the maintenance dose rate can be individualised to achieve a
specific target conc. A single conc cannot estimate an AUC. It can
estimate clearance (and you can derive AUC if you wish but that is
unnecessary because MDR comes directly from Clearance and Target Conc).
If you have several concs then you can calculate an AUC and use that to
estimate clearance.
Measuring two concs e.g. 'peak' and 'trough' allows a more precise
estimate of PK parameters. The point of measuring the concs is to
estimate clearance NOT because the MEASURED concs at particular times
are themselves are related to outcome.
Outcome should to be related to the target conc. For almost all
drugs the target conc is still something of a guess but outcome for
vanco may be related more closely to average steady state conc
[or AUC if you wish - they are equivalent] and thus Clearance is
the parameter you need to estimate to individualise dose.
If you only measure one conc then a mid-dosing interval conc will be
closer to the average conc and thus more readily related to clearance. A
trough conc implicitly relies more on assumptions about volume of
distribution than the mid-point conc.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html
Back to the Top
Cathy, I hope that this is useful to you:
Cathy Heyneman wrote:
>
> PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
> Hello all!
>
> I got such a wonderful response to my Chiou dilemma (thanks to all who
> responded!) I thought I'd see if my luck is still holding. : )
>
> 1. Regarding vanco kinetics, our instructor gives the following equation:
>
> Kel = 0.0044 + 0.00083(CrCl)
>
> I can't find this in any of my kinetics resources, and it gives a very
> different answer from the more commonly used Kel = ln(Cp1/Cp2)/time. So my
> question is, is this a valid equation, and if so, is CrCl expressed in
>ml/min?
>
> 2. Is it necessary to wait 1.5 half-lives before drawing the first vanco
> blood level?
>
> 3. If your vanco infusion is given over 2 hours instead of 1 hour, do you
> still need to wait a full 3 hours to account for the distribution phase
> before drawing a peak?
> The first equation relates vancomycin elimination rate (in 1/h) to
>creatinine clearance
in ml/min, and originates from Figure 2 of a paper by Matzke and
coworkers(Matzke et al
1984). We have successfully utilized this equation in a pharmacy based
program designed
to individualize initial doses of vancomycin for patients at the Buffalo
General
Hospital.
The second equation requires administration of the drug and the acquisition of
appropriately timed plasma concentrations. However, this approach has the
obvious
advantage of allowing the direct estimation of the elimination of vanco (or
any other
drug) in the patient. We also make use of this equation to aid in the
adjustment of
vanco doses to achieve desired plasma concentrations (i.e., follow-up).
The relationship of vancomycin concentrations to therapeutic effects and the
pharmaco-economic benefits and of vancomycin therapeutic drug monitoring
have been
questioned in the literature(Cantu et al 1994; Pryka et al 1991). However,
two papers
have been published which suggest that PK-based dosing has
pharmaco-economic benefits.
The first paper, by Lake and Peterson in 1988, claims that PK-based
initiation of vanco
therapy may lead to dramatic reductions in drug acquisition costs(Lake &
Peterson 1988)
(this has been our experience at BGH). The second paper, which has just
been published,
indicates that vancomycin TDM may reduce overall therapy costs by
decreasing the
incidence of vancomycin nephrotoxicity(Fernandez de Gatta et al 1996).
At BGH, we obtain peak vancomycin concentrations 1 hour after the end of a
1 or 2 hour
infusion of vanco (we use 2 hour infusions for patients receiving doses
greater than 1g
or for patients who develop =91red neck=92 syndrome).
Hope that this helps.
Joseph Balthasar, Ph.D., Rph
Clinical Assistant Professor, SUNY at Buffalo, Department of Pharmaceutics
Cited papers:
Cantu, T. G., Yamanaka-Yuen, N. A., Lietman, P. S. (1994) Serum vancomycin
concentrations: reappraisal of their clinical value. [Review]. Clinical
Infectious
Diseases 18: 533-43
=46ernandez de Gatta, M. M., Calvo, M. V., Hernandez, J. M., Caballero, D.,
San Miguel, J.
=46., Dominguez-Gil, A. (1996) Cost-effectiveness analysis of serum vancomycin
concentration monitoring in patients with hematologic malignancies. Clinical
Pharmacology & Therapeutics 60: 332-340
Lake, K. D., Peterson, C. D. (1988) Evaluation of a method for initiating
vancomycin
therapy: experience in 205 patients. Pharmacotherapy 8: 284-6
Matzke, G. R., McGory, R. W., Halstenson, C. E., Keane, W. F. (1984)
Pharmacokinetics of
vancomycin in patients with various degrees of renal function.
Antimicrobial Agents &
Chemotherapy 25: 433-7
Pryka, R. D., Rodvold, K. A., Erdman, S. M. (1991) An updated comparison of
drug dosing
methods. Part IV: Vancomycin. [Review]. Clinical Pharmacokinetics 20: 463-76
Back to the Top
I have always thought that a peak taken after the distribution
phase and in the elimination phase (i.e. at least 2 h post
vanco infusion) could be used with a trough to get a fairly dood
idea of T1/2 elim.
>PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
>> Why draw a peak any way? Vanco peaks have no real impact on outcome, and
>> are difficult to interpret due to the issues you are pointing out here. I'd
>> suggest either monitoring concentrations using troughs only (goal: 10-13
>> mg/L) or using a midpoint concentration (goal: 15-19 mg/L) to estimate AUC
>> and hence daily dose.
>
>I generally agree with the above but have a minor philosophical quibble.
>IMHO the point of measuring one or more concs is to estimate clearance so
>that the maintenance dose rate can be individualised to achieve a
>specific target conc. A single conc cannot estimate an AUC. It can
>estimate clearance (and you can derive AUC if you wish but that is
>unnecessary because MDR comes directly from Clearance and Target Conc).
>If you have several concs then you can calculate an AUC and use that to
>estimate clearance.
>
>Measuring two concs e.g. 'peak' and 'trough' allows a more precise
>estimate of PK parameters. The point of measuring the concs is to
>estimate clearance NOT because the MEASURED concs at particular times
>are themselves are related to outcome.
>
>Outcome should to be related to the target conc. For almost all
>drugs the target conc is still something of a guess but outcome for
>vanco may be related more closely to average steady state conc
>[or AUC if you wish - they are equivalent] and thus Clearance is
>the parameter you need to estimate to individualise dose.
>
>If you only measure one conc then a mid-dosing interval conc will be
>closer to the average conc and thus more readily related to clearance. A
>trough conc implicitly relies more on assumptions about volume of
>distribution than the mid-point conc.
>
>--
>Nick Holford, Dept Pharmacology & Clinical Pharmacology
>University of Auckland, Private Bag 92019, Auckland, New Zealand
>email:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
>http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html
The UK NEQAS for Antibiotic Assays is provided by:
Department of Microbiology, Southmead Health Services NHS Trust
Bristol BS10 5NB, UK.
Tel INT+UK+117 9595653 Fax INT+UK+117 9593217
http://www.ibmpcug.co.uk/~lwhite/index.html
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Nick-
I think we're in agreement. We obtain a single concentration midway in the
doing interval because 1) it provides some estimate of Cl; and 2) it's the
most cost-effective way to obtain some useful information. Obviously more
concentration points will allow for better estimates of AUC/Cl, but I doubt
this helps clinically.
At 10:28 AM 12/5/96 -0600, you wrote:
>PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
>> Why draw a peak any way? Vanco peaks have no real impact on outcome, and
>> are difficult to interpret due to the issues you are pointing out here. I'd
>> suggest either monitoring concentrations using troughs only (goal: 10-13
>> mg/L) or using a midpoint concentration (goal: 15-19 mg/L) to estimate AUC
>> and hence daily dose.
>
>I generally agree with the above but have a minor philosophical quibble.
>IMHO the point of measuring one or more concs is to estimate clearance so
>that the maintenance dose rate can be individualised to achieve a
>specific target conc. A single conc cannot estimate an AUC. It can
>estimate clearance (and you can derive AUC if you wish but that is
>unnecessary because MDR comes directly from Clearance and Target Conc).
>If you have several concs then you can calculate an AUC and use that to
>estimate clearance.
>
>Measuring two concs e.g. 'peak' and 'trough' allows a more precise
>estimate of PK parameters. The point of measuring the concs is to
>estimate clearance NOT because the MEASURED concs at particular times
>are themselves are related to outcome.
>
>Outcome should to be related to the target conc. For almost all
>drugs the target conc is still something of a guess but outcome for
>vanco may be related more closely to average steady state conc
>[or AUC if you wish - they are equivalent] and thus Clearance is
>the parameter you need to estimate to individualise dose.
>
>If you only measure one conc then a mid-dosing interval conc will be
>closer to the average conc and thus more readily related to clearance. A
>trough conc implicitly relies more on assumptions about volume of
>distribution than the mid-point conc.
>
>--
>Nick Holford, Dept Pharmacology & Clinical Pharmacology
>University of Auckland, Private Bag 92019, Auckland, New Zealand
>email:n.holford.aaa.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
>http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html
Back to the Top
> I have always thought that a peak taken after the distribution
> phase and in the elimination phase (i.e. at least 2 h post
> vanco infusion) could be used with a trough to get a fairly dood
> idea of T1/2 elim.
That is correct. And with a little bit of extra work you can estimate
what you really need to know to adjust dosing i.e. the clearance.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html
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