From: dyer@spdcc.com (Steve Dyer)
Newsgroups: sci.med
Subject: Re: azithromycin?
Date: 14 Dec 92 07:57:20 GMT
Article-I.D.: spdcc.1992Dec14.075720.15610
Organization: S.P. Dyer Computer Consulting, Cambridge MA

In article <1992Dec13.172917.525@news.wesleyan.edu> RGINZBERG@eagle.wesleyan.edu (Ruth Ginzberg) writes:
>I thought that the most interesting thing about azithromycin was its 5-day,
>rather than 10-day dosing reg.  However, I recently saw a "thing" on Lifetime
>Medical TV (which, at first, I thought was an "infomercial" for Zithromax, but
>apparently not...)

Trust your instincts.  It wouldn't surprise me at all if it were produced
by the manufacturer of azithromycin.

>which seemed to indicate that azithromycin was fundamentally different
>from its predecessors (in the erythromycin family) because ... (I
>wasn't sure I understood this part...) it accumulates between, rather
>than just inside of, tissue cells, & therefore keeps being absorbed by
>the cells for some time after discontinuation of the drug. (???) (Don't
>know if thats right.)

Azithromycin has in vitro activity against _roughly_ the same organisms
as erythromycin, give or take a few.  However, the drug is better
absorbed orally than erythromycin, causes less stomach distress, and is
resistant to degradation by the liver.  It also is less likely than
erythromycin to interfere with the metabolism of many common drugs
(remember the Seldane warning.)  It is more lipid soluble and can
therefore penetrate into certain cells that erythromycin can't.  In
fact, the drug is rapidly redistributed into tissues and white blood
cells where it serves as a repository.  Its tissue 1/2-life is about 3-4
days.  This allows less frequent dosing (once a day or less frequently)
than erythromycin (4x/day), and explains why a 5-day course of
treatment can be as effective as 10 days of erythromycin.

Clarithromycin is a similar erythromycin derivative which affords twice
a day administration, and has many of the same nice features (good oral
absorption, prolonged serum levels, few drug interactions and good GI
tolerance.)  It doesn't show the same peculiar tissue pharmacokinetics
as azithromycin, however.

One or the other of these drugs also show some activity in some unusual
infections which aren't well treated at present, and in which
erythromycin wouldn't be effective, such as MAI-complex, leprosy and
pneumocystis, depending on the drug.  This is probably due to an
increase in their antibiotic spectrum and better tissue penetration
allowing better access by the drugs.

>My ignorance in cell biology is now on full display (sorry), but I'm
>curious to know whether this is a real breakthrough in delivery of the
>drug, or in knowledge of bioavailability, or cell metabolism, or is it
>just new w.r.t.  this particular family of drugs, or is this just a
>bunch of hype being spewed out by the salescritters who are trying to
>make a modest new drug sound much more interesting than it actually is?

For most run-of-the-mill infections, the drug is a modest advance.  If
erythromycin works well and is tolerated OK (true in the majority of
cases), there is absolutely no reason to prescribe azithromycin (or the
other new macrolide, clarithromycin).  There is a big difference in
price between the old and new drugs, even after correcting for the
daily dose and length of treatment.  Of course, for those infections
where the special properties of these drugs can be exploited, they may
be quite useful.  Perhaps in 10-15 years or so when the patents expire,
and their prices plummet, these might be routinely prescribed instead
of erythromycin.  Of course, by that time, too, there should be a good
deal of clinical experience with these drugs as well and their adverse
reactions (if any) well characterized.  Not that they seem to be any
more toxic than erythromycin is from what we know now, but it isn't
very good practice to suddenly start using a new drug when a less
expensive old drug will do as well, and whose side effects are well
understood.

-- 
Steve Dyer
dyer@ursa-major.spdcc.com aka {ima,harvard,rayssd,linus,m2c}!spdcc!dyer
Newsgroups: sci.med