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Good Afternoon:
I need information about the "typical" metabolism rate for
caffeine: half-life, or complete metabolism following a single
ingestion. Other than some referent that can be deemed
"typical", the source for the caffeine (e.g., a beverage) is
irrelevant for my purpose as are moderating factors (e.g., body
wt, basal metabolism rate). My sources give me all the
information I want about caffeine effects EXCEPT for how long it
takes the body to wash the stuff out of the system. I need to
document this information in some way, so reference to a text
and/or the source the text used also is needed.
I am initiating a research project using transcranial Doppler
(TCD) to measure cerebral blood flow velocities, and it is quite
likely that my subjects (students) will have consumed a caffeine-
bearing beverage. Caffeine is vasoactive, but the TCD literature
is silent with regard to how caffeine may (or may not) influence
CHANGES in blood velocity following a single ingestion. In the
absence of this information, my alternative is to ask subjects to
abstain from caffeinated beverages prior to testing (but, for how
long?). Hence my need for this information.
I can be reached at the e-mail address within my signature box.
Thanks for your help.
AER
:
- - - - - - End of Message From: - - - - - - - - - - - - - - -
A.E. (Robin) Roberts, Ph.D. e-mail: aroberts.aaa.catawba.edu
The Department of Psychology phone: [704] 637-4385
Catawba College FAX: [704] 637-4444
Salisbury, NC 28144 USA
* * * "Data prevail, not men" (Bachrach, 1972) * * *
================================================================------------------------------
Date: Thu, 28 Aug 1997 10:04:33 -0500
From: "David Nix"
Subject: Vancomycin extended interval dosing
I would be cautious about extrapolating the success of aminoglycoside
pulse dosing to vancomycin. Aminoglycosides are quite different in
pharmacodynamic properties than vancomycin. Aminoglycosides exhibit
1. Pronounced concentration-dependent killing
2. Significant post antibiotic effect for gram negative organisms
3. Adaptive resistance
Thus, the primary goals of dosing are to achieve a high Cmax to MIC
ratio and allow concentrations to fall below the MIC for a period of
time before redosing. The AUC relative to the MIC is also
correlated with efficacy. Toxicity with aminoglycosides may be
lower with pulse dosing as compared to more frequent dosing. Pulse
dosing is supported by a large number of small clinical trials.
Despite the success, I remain concerned about 2 groups of patients
that are treated with pulse dosing (once a day aminoglycoside). The
first group is young patients that eliminate the aminoglycoside very
quickly (t1/2 ~ 1.5 to 2.5 hours). These individuals have a
prolonged "drug-free" period of >12 hours which greatly exceeds the
post antibiotic effect period. Patients with impaired renal
function are also sometimes allowed to have prolonged periods with
low sub MIC concentration. However, this has not been a major
problem since these patients are typically treated with an
aminoglycoside in combination with a beta-lactam agent. The second
group of patients includes patients with mildly impaired renal
function. Once-a-day treatment is sometimes used in patients where
the trough concentration is still detectable (>0.5 mg/L). These
patients are often getting 2-3 times the exposure in terms of AUC
than they would have received with traditional dosing strategies.
Increased risk of toxicity may be a problem here.
Vancomycin is more like a beta-lactam agent than an aminoglycoside
in terms of pharmacodynamic properties. Bacterial killing is not as
concentration-dependent as aminoglycosides. Post antibiotic effect
is present - this is true for most antimicrobials against
gram-positive bacteria. However, we know far less about
pharmacodynamic properties that determine efficacy. Moellering
suggested maintaining an average steady-state concentration of about
15 mg/mL, and most other dosing methods have been consistent with
this strategy. There are administration problems with vancomycin -
specifically, larger doses are more frequently associated with red
man syndrome. Slower infusion rates help but do not always prevent
the problem. Although, the data are not very convincing, ototoxicity
may be related to high peak concentrations. With vancomycin, we
often rely on single drug coverage for Staphylococci. Even for
Enterococci, aminoglycosides are used primarily for synergy.
I suggest that extended interval vancomycin (i.e. once daily in
patients with renal dysfunction) is clearly a research issue with
little data to support it. I would be concerned about very high peak
concentrations and prolonged "drug-free" intervals. Any research
should include studies to determine how this dose change affects
efficacy as well as the development of antimicrobial resistance
David Nix
University of Arizona College of Pharmacy
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> Reply-to: PharmPK.-at-.pharm.cpb.uokhsc.edu
> Date: Wed, 27 Aug 1997 11:37:58 -0500
> From: "Dr. Al Roberts"(by way of
>David_Bourne)
> To: Multiple recipients of PharmPK - Sent by
>
> Subject: Request for Information
Dr Roberts,
Mean (SD) caffeine half-life in adults is about 5(2) hr, clearance
is about 1.5 (0.5) ml/min/kg and V 0.6 (0.02) l/kg, and is almost
totally metabolised by liver; 1(0.5)% excreted unchanged.
I would probably withold caffeine beverages (don't forget
OTC preparations, cola drinks, etc) for 10 half-lives (i.e. 2 days).
if your coffee drinkers can stand the withdrawal symtpoms!
Blanchard & Sawers. J. Pharmacokinet. Biopharm. 1983, 11,
109-126.
Busto et al. Clin Pharmacokinet. 1989, 16, 1-26.
Hope this helps,
BC
> PharmPK - Discussions about Pharmacokinetics
> Pharmacodynamics and related topics
>
> Good Afternoon:
> I need information about the "typical" metabolism rate for
> caffeine: half-life, or complete metabolism following a single
> ingestion. Other than some referent that can be deemed
> "typical", the source for the caffeine (e.g., a beverage) is
> irrelevant for my purpose as are moderating factors (e.g., body
> wt, basal metabolism rate). My sources give me all the
> information I want about caffeine effects EXCEPT for how long it
> takes the body to wash the stuff out of the system. I need to
> document this information in some way, so reference to a text
> and/or the source the text used also is needed.
>
> I am initiating a research project using transcranial Doppler
> (TCD) to measure cerebral blood flow velocities, and it is quite
> likely that my subjects (students) will have consumed a caffeine-
> bearing beverage. Caffeine is vasoactive, but the TCD literature
> is silent with regard to how caffeine may (or may not) influence
> CHANGES in blood velocity following a single ingestion. In the
> absence of this information, my alternative is to ask subjects to
> abstain from caffeinated beverages prior to testing (but, for how
> long?). Hence my need for this information.
>
> I can be reached at the e-mail address within my signature box.
>
> Thanks for your help.
>
> AER
> :
> - - - - - - End of Message From: - - - - - - - - - - - - - - -
> A.E. (Robin) Roberts, Ph.D. e-mail: aroberts.at.catawba.edu
> The Department of Psychology phone: [704] 637-4385
> Catawba College FAX: [704] 637-4444
> Salisbury, NC 28144 USA
> * * * "Data prevail, not men" (Bachrach, 1972) * * *
> =================================================================>
>
> Also see: http://www.cpb.uokhsc.edu/pkin/pkin.html
>
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Bruce CHARLES, PhD
School of Pharmacy
The University of Queensland
Brisbane, Qld, Australia 4072
Telephone : +61 7 336 53194
Facsimile : +61 7 336 51688
Email : Bruce.Charles.aaa.pharmacy.uq.edu.au
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)