Back to the Top
I would like to hear some comments regarding the following data.
For a NCE, it showed 100% bioavailabiliity in the rat when 20% captisol
was used as IV and PO vehicles. This NCE was taken to the dog for
bioavailability estimation later. The formulation was changed to
suspension in 0.5% methylcellulose for PO and the IV formulation
remained the same as for the rat. The bioavailabilyty in dog dropped
to less than 5%. My speculations are: 1) captisol artificially
enhanced the bioavailability in rat and the results will not be
relevant. 2) metabolism is different b/w rat and dog. But it has to
be a REALLY BIG difference.
Attached below is previous discussion I brought up a couple of months
ago. Just for your reference.
[Deleted - the previous discussion was entitled Captisol 20% as IV and
PO vehicle in early rat PK study - db]
Thanks in advance for sharing your thoughts or experience.
Zhaoyang LI, Ph.D.
Pharmacokinetics and Drug Metabolism
Back to the Top
My guess is that you have a solubility limited absorption problem.
Captisol is a GREAT solubilizing agent so your dose was probably a
solution (and presumably remained a solution as well). However, 0.5%
methylcell is most likely a suspension. This solubility difference
could make the difference between 5% and 100%.
Bruce Tomczuk, PhD
3-Dimensional Pharmaceuticals, Inc.
a wholly owned Johnson & Johnson company
665 Stockton Drive
Exton, PA 19341
(610) 458-6058 direct
(610) 458-8258 fax
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (email@example.com)