Solvent for oral administration of test drugs - DW or PBS or Saline (Oct/26/2008 )

Dear friends,
I am planning to do experiment on rats regarding experimental therapeutics. The test compound will be administered orally by using oral gavage. My question is which solvent is best for the oral doses and why??..DW or PBS or Saline? What is the appropriate volume (drugs in solevent) to the rats weighing approximately 200 g ? Do I need to calculate dose by weighing the rats (for example if I wish to give 2 doses/day)??

anticipating to know your suggestion and experience.

Thapa

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Hello,

We do a lot of oral gavage administration to mice in the context of experimental anticancer therapeutics.

Appropriate volume?: We give 10 microL/gram body weight (i.e. 10 ml/kg) to our mice. The most common volume guideline for rats that I've seen is 20 ml/kg as a maximum. Thus, a 200 g rat would get no more than 4 ml of drug. The idea is to give a volume that is not so large that it forces open the pyloric sphincter or causes reflux into the esophagus. Your local IACUC or lab animal vet would be a good source of info, since it is their guidelines that you must follow.

Moreover, we dose based on the individual animal's true body weight (BW); i.e. we measure BW once/week and then adjust dosing volume for each animal accordingly. Alternatively, you could dose the animals based on the average BW in the group. The drug dose will vary slightly among animals, but it may be easier in that you will administer the same volume to each animal.

Which solvent/vehicle?: The selection of vehicle/formulation is an entire field unto itself of which I am not an expert. My impression is that, if the agent is water-soluble, then any of the 3 you mentioned will work - I've seen all 3 used in the literature. Our agents are generally very hydrophobic, so we dose as a suspension in a methylcellulose/Tween 80-based vehicle. Others have used PEG and cyclodextrin (CD). Tween (polysorbate) is very safe for the rodent; PEG can have toxicities at higher doses; CD may reduce absorption of the drug if it complexes too tightly with the drug.

Hope this helps,
SK

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Hello,
Really a nice explaination SamOH. Thank you for sharing your knowledge and experience with us.

Further, I will be glad to know if there is difference in using buffer, saline and DW??

Once again thank you so much SK .

regards,
Thapa

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Thapa,

I'm not aware of any differences among the three vehicles you mentioned with respect to oral delivery. I figure that your choice will depend on (i) the compound itself (will these vehicles affect stability, solubility...?) and/or (ii) standards in the literature for the compound (if its use has been published).

Good luck!
SK

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I was just curious to know whats the logic to select the solevents. Thank you SK for your reply, you have given several hints again to think about nature of compound and publication related to that particular compound. ...I think these are really worthy.

Thanks again,
Thapa

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