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The following message was posted to: PharmPK
Dear all:
In the latest version of the antibiotic discussion Hans Proost wrote:
> OK, but the higher the concentration, the more rapid the killing of
> bacteria, until the effect levels off at high concentrations.
While that statement may be true for drugs whose effect is within the
same compartment from where they are measured, what principles do we
have that discriminate between desirable (therapeutic) and undesirable
(toxic) target effects, especially when drug levels are not available at
the target site?
--
Professor Walter Wolf, Ph.D.
Distinguished Professor of Pharmaceutical Sciences
Director, Pharmacokinetic Imaging Program
Department of Pharmaceutical Sciences, School of Pharmacy
University of Southern California
1985 Zonal Ave., Los Angeles, CA 90089-9121
E-Mail: wwolfw.-at-.usc.edu
Telephone: 323-442-1405
Fax: 323-442-9804
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The following message was posted to: PharmPK
The point Dr. Wolf makes is a crucial one in all pharmacology-
toxicology.
It is a question of threshold: when, why, and how does a salubrious
agent
become toxic - and vice versa?
This subject matter pertains to the Arndt-Schulz-Rule, to Hormesis.
It has a
long history, albeit too often neglected by pharmacologists - since
methods
of high resolution and high sensitivity are required.
I have reviewed this subject in an article in Drug Metabolism
Reviews, volume
37 (4), now in press, entitled: The Dose Makes the Medicine.
Walter E. Stumpf
Chapel Hill, NC
walterstumpf.com
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