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Dear Wagner
Hello!
We are doing pre-clinical pharmacokinetic studies of new
chemical entity whose oral dose in rats are 30 and 60
mg/kg. We have a problem with 60 mg/kg dose because the
plasma concentration versus time profile has shown a
different behavior from that 30 mg/kg dose.
Sample times: 0, 15 min, 30 min, 45 min, 1h, 2, 4, 6, 8,
10 and 12h.
The first Cmax was obtained at 45 min and the second Cmax
at 6 hours. After the first Cmax has been reached, the
profile has shown a straight line and after that it began
to arrise again.
Cmax2 bigger than Cmax1
When was administered 45 mg/kg dose the plasma
concentration versus time profile was the same that 60
mg/kg and different from that 30 mg/kg one.
I do not know what happened. Enterohepatic recirculation,
different sites of absorption?
I wait your help and reply.
Kindly also provide relevant references.
Leandro Tasso,
Laboratório de Farmacocinética
Programa de Pós Graduação em Ciências Farmacêuticas
90610-000 RS-Brasil
+51 3316 5215
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The following message was posted to: PharmPK
hi Tasso
firstly were all time points from a single animal? if not then the
sampling
design may influence your PK profile. inorder to clearly distinguish
enterohepatic recycling, one needs to administer an I.V dose. Do you
have a
PK profile after an I.V dose? if you see a double peak after an I.V
dose too
then it is more likely that the molecule is undergoing enterohepatic
recycling otherwise there could be other possibilities.
hope this helps
All the Best
manish
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The following message was posted to: PharmPK
Hello Tasso
It is possible that there is a saturable absorption from the first site
of drug
absorption which is reflected in early Cmax. This could contribute to
the
differences you observe at 30 mg/kg vs 45,60mg/kg. You can check this
by doing
insitu absorption studies based on the physicochemical properties of
your
molecule.
Venkatesh Atul Bhattaram
Post-Doctoral Fellow
University of Florida
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