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The following message was posted to: PharmPK
Dear All,
My name is Ravi Kanth Bhamidipati. I am working as a Senior
Pharmacologist in Department of Drug Metabolism and Pharmacokinetics of
Dr. Reddy's Laboratories Ltd.India. I am having few doubts in the area
of drug absorption. They are as follows:
1) What can be the probable reasons behind a compound showing species
differences in the oral bioavailability pattern.Can we attribute the
difference to the difference in the expression of transporter proteins
across the species?
2) Can transporter proteins show any route specific difference in the
efflux of a particular compound.
Thanking you,
Yours Sincerely
Ravi Kanth Bhamidipati
Ravi Kanth Bhamidipati
Senior Pharmacologist
Dept.of Drug Metabolism and Pharmacokinetics
Discovery Research Division
Dr.Reddy's Laboratories Ltd.
Bollaram Road , Miyapur
Hyderabad - 500 050
Andhra Pradesh
India
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Dear Ravikanth,
Your first question requires whole lot of explanation but due to space
and
time constraints I have given below a small note on that as :
Drug absorption is influenced by many physiological factors, but it
depends
also on physico chemical characteristics of the drug itself.
The
physiological factors include gastric and intestinal transit time,
blood
flow rate, gastrointestinal pH, and first pass metabolism.
Physiological
factors are subject to species variation and hence differences in
oral
bioavailability could be because of differences in the
physiological
factors mentioned above. As you have mentioned the involvement
of
transporter proteins, could be one of the reasons for the
observed
difference in oral bioavailability in different species of exptl
animals.
To attribute it to transporter proteins, you need to rule
out/eliminate
other possibilities.
For your second question answer could be partly yes, if your
drug is
metabolized by intestinal or hepatic enzymes, metabolic enzyme
induction is
a dose dependent and time dependent phenomenon for hepatic and
intestinal
enzyme induction. The intestinal induction appears to be independent of
the
route of administration when inducing agent is given at higher
dose.
Intestinal p-glycoprotein mediated transport also limits the
absorption of
orally administered drugs, where as it could have little
influence on
parenteral dose.
best regards,
ramakrishna bangaru
biopharmaceutics research
Dr.Reddy's Laboratories, Generics
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