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My name is Ravi Kanth.B. I am working as a pharmacokinetist in Dr.Reddy's
Research foundation, India. MY job out here is establishing pharmacokinetic
profiles of various molecules synthesized in our
Sir one month earlier I faced a peculiar situation while i was engaged
in carrying out Gender Variation Study of one of our research molecule. I am
giving a lucid description of the problem encountered.
Sir, it is the common practice here to first establish all the basic
pharmacokinetic parameters in male Wistar rats followed by in females. so
I carried out the the study of one of the molecule .-at-. 10mg/kg in males i=
that AUC was at around 18=B5g . Almost similar AUC was obtained when i=
out the expt. 3 to 4 times. Moreover dose proportionality also existed when
the studies are carried out at log doses.
So after completion of the study in males i started Gender Variation
Study. Normally we take 6 animals belonging to each sex in two different
and dose them and then collect the blood samples at regular intervals and
carry out HPLC analysis.To my surprise I found that there was a drastic
decrease in the AUC ( i.e 8=B5g approx)in males when kinetic study was=
out in the proximity of females. When I again carried out the study in the
absence of females the AUC was within the range which i got earlier.
CAN YOU GIVE ANY POSSIBLE EXPLANATION FOR THIS PECULIAR BEHAVIOUR.
ARE PHERAMONES PLAYING ANY PART HERE?
Please send in the possible explanations to
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Dear Mr Ravikanth,
Gender variation is a known entity in
clinical pharmacokinetics.For example as compared to males,females do not
metabolise alcohol as well because of absence of lactic dehydrogenase
enzyme,which is present in gastric juice in males.Hence the absorption is
more and higher blood levels are achieved in females.
Secondly during menstruation due to higher levels of oestrogen in
females,the gastric emptying is slower and this can make a difference in
thirdly due to females possessing lesser amount of lean body mass and more
of subcutaneous fat,there is a difference as regards distribution of drugs
in the body compartments.
These factors apart there are basic differences in the physiology of females
at times of pregnancy when the apparent body volume increases manifold
hence affecting drug distribution.also hormonal changes are excessive at
These differences can be expected in other species as well.
You have raised an interesting point about increased lipid absorption during
stress which may affect lipophilic drug absorption.Do let me know what
feedbak you recieve on this .
Dr Amit Taneja
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