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I am working on a water insoluble NCE. Need to do PK study in Guinea
Pigs. Can anyone tell me how the following formulation is tolerated
in GineaPigs via IV.
10% DMSO
10% Ethanol
80% PEG400
Thanks.
Amit Shah
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Hi amith
Still you are in the limits only. it could tolerate easily. You could
also use
10% cremophor or 10% EtOH final volume with saline .
Thanks.
A.karthik
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The following message was posted to: PharmPK
Hi Karthik,
Thanks for the reply. I tried to search the literature if there is
any tox data on Guinea Pig IV but could not find one. Do you have any
literature which you can share?.
In my formulation other than DMSO and Ethanol, I am also worried
about 80% PEG because higher dose of PEG causes cardiac problems in
canine.
Thanks.
Amit
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The following message was posted to: PharmPK
I missed the orginal message but this may help:
International J of Toxicology 2006, 25, 499-521 by Gad and Cassidy
list many vehicles, routes, species used in preclinical studies.
There is data on G. Pigs for PEG and DMSO
-T
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Dear Amit,
I have an additional question for you : did you check the stability
of your formulation upon dilution in a pH7.4 buffer?
Once again I am concerned that a massive precipitation may occur at
the injection point ...and your PK parameters may not be relevant if
such an event takes place.
Regards,
Frederic Doc
fdoc.-at-.acriter-consulting.com
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The following message was posted to: PharmPK
> You could
> also use
> 10% cremophor or 10% EtOH final volume with saline.
> A.karthik
I certainly pretty much prefer Karthik's formulation approach.
Regards,
Frederic Doc
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The following message was posted to: PharmPK
H Fred,
My earlier target conc was 10 mg/mL of 1 API which did not precipitate
at physiological pH. This study was carried out in rats. My new target
conc. is 20 mg /mL with a 1:1:1 mixture of 3 closely related compounds
(including the one that I tested earlier). Therefore as you suggested, I
will need to check the precipitation potential in a pH 7.4 media.
In one of the other study that we did previously, cremophor el caused a
lot of nausea and discomfort in dogs. Therefore I am not sure whether it
will work for guinea pigs.
Please comment.
Thanks
Amit
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The following message was posted to: PharmPK
Dear Amit,
Cremophor EL is well-known for its effects in dogs. I am not sure of
the reactions with guinea pigs because I did not have the opportunity
to work on this species.
Regarding precipitation I am quite surprised that you did not face
any issue with such a formulation but that's a good point if you are
comfortable with it.
Regarding the use of cassette-dosing (simultaneous dosing of 3 APIs)
I suppose that you are in a "screening mode" assuming that there is
no competition between the APIs relating to distribution or
elimination for instance.
Cheers,
Frederic DOC, PharmD, MS in Biopharmaceutics
fdoc.-at-.acriter-consulting.com
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