PharmPK Discussion - Co-delivery of protein and small molecules

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On 8 Mar 2005 at 10:44:19, "Noelle Williams" (Noelle.Williams.at.UTSouthwestern.edu) sent the message


Hi,

I have a small molecule that synergizes in vitro with a protein ligand
for a cell surface receptor for inhibiting tumor cell line growth.  I
am doing some early proof of principle studies in a xenograft model and
was wondering if it would be a problem to deliver the two together in a
single IV injection.  I need to do daily IV injections and do not think
I am capable technically of doing two IV injections daily to a bunch of
mice.  I could try IP delivery of one or the other, but I was assuming
I would get better compound and protein levels if I gave both IV.
There is no reason to believe that the small molecule would interact
specifically with this protein - I just wondered if there was a danger
of co-delivery affecting how each would perform in vivo.  I'm thinking
I should avoid this, but I wanted a better rationale than my own
intuition.

Thanks,

Noelle

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On 9 Mar 2005 at 06:10:59, pharmaco kinetics (phar_res1.at.yahoo.com) sent the message


Hi Noelle,

If you are worried about the performace of individual agents in vivo,
well there can be a  possibility of pharmacokinetic as well as
pharmacodynamic interaction after administration of both the
agents.That depends of the properties of your small molecule as well as
protein. And you will come to know about it only after doing it.
And if just administering both of them simultaneuously intravenously is
your problem, you may opt for cannulation purposes. Even you can give
the small molecule by oral route if its use intended for oral
administration.
Is the small molecule you are administering water insoluble? If so, it
will really be a problem to administer both the small molecule and
protein in one IV injection.

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On 9 Mar 2005 at 15:55:58, =?ISO-8859-1?Q?Frederic_DOC?= (fredericdoc.-at-.netcourrier.com) sent the message


The following message was posted to: PharmPK

Noelle,

I suggest that you design a formulation where the molecule and the
ligand are solubilized. You check the absence of interaction and the
stability of the solution (by HPLC assay for instance). If everything
is OK (no trouble about physical chemical properties of the
formulation) you can dose this formulation with both the molecule and
the ligand.
Co-delivery is OK if there is no interaction leading to physical
chemical modifications between both entities. In that case one
formulation with both entities will show the same data as two
formulations dosed some seconds or minutes after.
Just a last comment : when you solubilize different entities you should
sometimes expect a decrease of solubility as compared to "solo"
solubilizations.
I'm sorry not to give you a better rationale to avoid co-dosing but
this is a good alternative as far as the stability and the absence of
interaction between entities are checked in such formulations.

Hope this helps,
Frederic

Frederic Doc
ACRITER - drug discovery consulting
Visit our web site at : www.acriter-consulting.com

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