Back to the Top
Hi,
Does anybody know if everted gut sac method (in Rat) can be used to
determine Peff . If it is used, how can we calculate the permeability?
It would be appreciated if you provide me some references.
Thank you
Parvin
email:parvinzm.at.yahoo.com
Phone: work: +98 (411) 339-2583
Back to the Top
The following message was posted to: PharmPK
One "old" reference shows how we used the everted sac. S Kaplan and S
Cotler, J Pharm Sci, vol 61, No 9, Sept 1972. Pages 1361-1365
S Cotler
Back to the Top
Hi All,
In calculating the Papp values I have a total mass of my compound in
donor solution at t=0 is 475 ng; t=120 mins 53ng.
Whereas, in the receiver solution at t=0 0 ng and at t=120 mins 108 ng.
There is a loss of my compound in the donor side after 120 mins.
My question is when I calculate Papp using Papp=(1/S.Co)(dQ/dt), is it
correct to compare with literature reported values for taxol, digoxin
etc. Because I dont know about the loss in the case of taxol and
digoxin. I get a better values than taxol and wondering my calculations
over estimate Papp.
Thanks in advance for your suggestion.
Lourdes
Back to the Top
The following message was posted to: PharmPK
Dear Colleague,
The following paper could be of help:
Terziivanov, D., I. Havlik and I. Janku. Evidence for
saturable component in isoniazid transfer across rat
small intestine in vitro. J Pharm Pharmacol., 1982,
34, 817-819.
The method discriminates saturable from linear
component in intestinal transport when it exists.
Regards,
D. Terziivanov
Dimiter Terziivanov, MD,PhD,DSc, Professor
Department of Clinical Pharmacology and
Pharmacokinetics,
Clinic for Therapeutics and Clinical Pharmacology,
Univ Hosp "St. I.Rilsky",
15 Acad. I. Geshov st, 1431 Sofia, Bulgaria
Tel:(+ 359 2)8510639;(+ 359 2)5812 828.
Fax:(+ 359 2)8519309. e-mal: terziiv.-a-.yahoo.com
Back to the Top
The following message was posted to: PharmPK
Dear Lourdes,
That is the question all people estimating permeability of poorly water
soluble drugs end up with!!
Papp is generally calculated on the basis of initial donor concentration
which is fine for moderate to high soluble drugs. But, while estimating
Papp
for lipophilic drugs one would experience loss in the donor chamber as
poor
aqueous solubility of these drugs lead to either precipitation or
non-specific adsorption, which is what your problem is.
In such cases its not correct to calculate Papp based on either the
initial
or final donor concentration as you might end up in under/over
estimating
it. You have two ways to go about this:
1. Try and monitor the loss in the donor chamber and if the loss is
gradual
and throughut the experimental period you cannot do much about it. But
if
the loss is noticed in the first 30min or 1 hour and then stabilised
you can
calculate the Papp based on the this plateu concentration. Also you
need to
take the flux (dQ/dt) from the time points that fall in this plateu
range.
2. You can either try adding co-solvents (such as dmso, ethanol) or
surfactants (such as PS-80, Cremophor EL etc) to avoid or limit the
loss.
However, you need to be cautious as these additives might change the
thermodynamic activity of the drug, inhibit efflux pumps or alter
membrane
integrity.
NOTE: While estimating the loss dont forget to account for the drug
in the
tissue/monolayer for mass balance.
Hope this helps.
Best luck!
Kasiram.
Back to the Top
Dear Kasiram,
Thanks for your explanation. We are trying to rank order the compounds
absorption potential from calculating the Papp on caco-2
model. Therefore, measured t=0 and t=120 mins of donor and receiver
solutions. For some compounds have mass balance over 100% sometimes
closer to 200-700%. I know most of the compounds are hydrophobic and
sticking to the plastic vials.
My question is when a mass balance is greater than 100%, what ever
adsorbed in the donor side is getting released as the compound diffused
to the receiver side, at t=120 mins. And therefore, Papp is over
estimated in those cases.
Thanks
Lourdes
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)