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Dear all:
My question is related to how to clasify AZTaccording the BCS. From
in vitro studies it is fairly easy to demonstrate that AZT is a High
Solubility drug. However, regarding Permeability, this drug has an
absolute bioavailability (F) of approx. 65%, however, PDR reports
that the urinary excretion is of about 90% of the administered dose
(~ 14% unchanged and the rest as metabolites).
I did not find reports of AZT being metabolized in intestine, thus,
could I suppose that if 90% of the administered dose is eliminated by
urine (and if AZT is not metabolized in intestine), that 90 % was
effectively absorbed? that the 65% of F was due to a ~ 35% hepatic
first pass metabolism? and finally that AZT is a highly permeable
drug?
Thanks and regards to all, Silvia Giarcovich (Diffucap-Eurand SACIFI,
Argentina)
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The following message was posted to: PharmPK
Dear Silvia
Your observations based on the available literature, particularly in the
absence of extra-hepatic metabolism, looks logical. It may require
confirmation by conducting human bioavailability to check all the
parameters of absorption and metabolism. But to qualify in BCS , the
current regulatory feedback says, that all these findings must be from a
statistically relevant sample size which may not be the case when the drug
is approved as NDA. Though there is lot of discussion on BCS, to my
knowledge, no single generic drug has been approved so far based on BCS. I
do not know similar observations from literature, for different drugs, may
be sufficient to claim biowaiver. I request FDA / other regulatory
authorities to throw some light on these issues.
Thanks and regards
Swaroop
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