PharmPK Discussion - Formulation for mouse PK study

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On 3 May 2004 at 11:13:19, "A P" (ap_pk_2004.at.hotmail.com) sent the message

Dear all
I have read the previous discussions on preclinical formulations with
much interest and would appreciate if anyone could provide further
input:
We will soon be performing some PK studies of a compound that is very
lipophilic in structure.
The compound will be administered to mice po and iv, using the SAME
vehicle for both routes if possible.
 From what i have read, I would prefer not to use cyclodextrins due to
likely
complexation or DMSO due to potential adverse effects.
I would greatly appreciate if anyone could provide me with a starting
point
Thanks
AP

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On 6 May 2004 at 14:57:13, Krishna Kumar Machavaram (Krishna.Machavaram.-a-.vcp.monash.edu.au) sent the message

Hai,
I think, selection of a suitable vehicle will be a very common and
serious problem for NCEs.
  For I.V. administrations, you can try a vehicle with either few drops
of tween 80  or 10 % DMSO in normal saline. It is also important how much
dose volume you are using for I.V dosings. You have to use lower dose
volumes in order to maintain lower concentrations of DMSO (preferably less than
10%) for I.V dosings where toxic effects can be minimised. I don't think
there will be a serious toxic effect when you use your formulation for single
dose PK studies with the above mentioned vehicles.If you didn't get a uniform
formulation with the above mentioned vehicles, then you may need to go
for a mixture of suspending, solubilising agents for a suitable formulation.
or you can reduce the dose where you can get a good formulation.
I am very sorry If I confused or scared you,
Thanks
krishna

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