Dear Group,Back to the Top
When a molecule is given by oral route in its free base and sodium salt
form, it was observed that the free base has lower AUC compared to the
But the steady state volume of distribution (Vdss/F) of the free base
was more compared to the salt form.
Is this difference in Vdss/F common for salt and free base of the same
molecule, if so why does this happen?
The reason behind asking this is, to the best of my knowledge even
though when a molecule given as a salt by oral route, only the free
drug (base) reaches the systemic circulation.
DMPK, Discovery Research
[free base has lower AUC; thus F, its bioavailability, is lower, thus
V/F is larger as you observe - in blood there will be a mixture of salt
and base depending on the pH/pKa - (see
http://www.boomer.org/c/p4/c12/c1202.html#js1 ) - db
On another note - my initial checking of email addresses was useful but
not as useful as I would like. I found a lot of people on vacation (Fri
pm ;-) but also found that the way I sent out the message interacted
with various spam etc. filters to loose some of its usefulness - with
your assumed permission I will send out one more test message later
today - last one for a few months at least - than you - db]
Dear Vinu,Back to the Top
Answer is there in your question itself. Lower AUC points towards low
relative bioavailability in comparison to your salt resulting in the
changes in denominator (F) which is then apparent as increased/decreased
Vdss. This could be due to number of reasons but most obvious one is
the improved solubility/dissolution of your salt form while the free
base might precipitate and you have poor absorption.
Hope this helps.
Manoj Khurana, Ph. D.
Post Doctoral Fellow
Pharmacokinetics Biopharmaceutics Laboratory,
University of Maryland Baltimore
Rm 503B, HSF-II Building
20 Penn Street, Baltimore, MD 21201
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