Back to the Top
I will be conducting a study of the effects of giving a dilute
concentration versus a standard concentration of a NMB. We will be
comparing onset times and duration. My question is, in theory, should
there be a difference, and if so what should it be? Keep in mind that
equal doses will be given. Is anyone aware of any studies pertaining to
any class of drug where differing concentrations but equal doses were
given?
Scott Farley
Back to the Top
Reply to Scott Farley:
If you already know the parameters for absorption, distribution,
binding, metabolism, and elimination of your drug, it would be a simple
matter to calculate (using any of a number of simulation packages) the
expected plasma concentrations for the two different dosing protocols
(1-short infusion, high concentration, 2-longer infusion, lesser
concentration; both delivering the same total dose). If the drug was
designed for a particular dosing scheme, a smaller concentration infused
for a longer time runs the risk of never reaching the target therapeutic
concentration. This could occur, for example, if drug metabolism or
elimination outpaced absorption.
If your situation is more complex, please repost to the list. Good luck.
Regards,
Bob
--
Robert D. Phair, Ph.D. rphair.-a-.ix.netcom.com
BioInformatics Services http://www.webcom.com/rphair
Partnering and Outsourcing for Computational Biology
Back to the Top
To answer your question: I don't expect any difference in onset time
and duration between a standard concentration and a dilute
concentration. If there is any effect, it will be small, and
unlikely to be revealed experimentally.
If a drug is administered intravenously, it will be diluted to a
considerable extent before it is transported via the arteria to the
muscles. This dilution will be more pronounced if a small volume is
injected, and less pronounced if a larger volume is injected. As a
result, the concentration profile in the arteria will be less affected
by the concentration of the injected solution. Although the steep
rise and fall of the concentration during the first minute may be
less pronounced than after injection of more concentrated solutions,
the average concentration in the arteria will be hardly affected, and
therefore also the net transport to the biophase.
However, this is theory, and it would be interesting to test this in
practice. I am not aware of studies performed in this topic, so I
also are interested in reactions by others.
It is not clear from your message why you want to perform such a
study. Is this a question relevant to anesthesiological practice, or
is it a purely scientific interest. Please give us more information
about the rationale behind your question.
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.at.farm.rug.nl
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)