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Dear all,
Is it feasible/ethical to administer daily intravenous boluses to
jugular cannulated rats where the drug is dissolved in
triethlyamine solvent at a pH of 9.0-10.0 for 7 day tox study?
Your comments much appreciated,
John
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The following message was posted to: PharmPK
i thinks is not feasible
TEA induces in vivo exposure headache, nausea and vomiting and pH
9-10 is not recommended.
Why don't you use another solvent or what about stability of your
drug in isotonic soution?
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Hello,
I can see that you can see from your animal experiments if they are
having vomiting and perhaps nausea but I wonder how do you measure or
know if rats are having headaches due to an in-vivo exposure of a
certain compound.
Thanking you, Sue
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Hi John,
The pH range you are aiming appears to be on the higher side. Blood,
due to its inherant buffering capacity can withstand administration
of solutions of higher or lower pH to some extent. The most important
aspect you forgot to mention in your mail is volume you are
administering. As the rat blood volume is ~ 6.0 ml, if the volume of
the solution you are administering is ~ 100 ul (~ 1.7 %), it should
be fine.
Hemolysis is sometimes observed during initial time points upon
intravenous administration. It is a very good marker suggesting
incompatability. In some cases hemolysis may be drug induced. As a
confirmation study you can inject your placebo and check the the
basis for that.
Hope this helps.
Good luck
Ravi
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Thanks for the message David. Our formulation people are having are
having trouble getting the drug dissolved in isotonic solutions. The
final concentration of triethlyamine in the solution is around 0.25
mg/kg.So typically a 250 gm rat would get 0.06 mg of TEA per day for
7 days. Do you think these levels would cause nausea and vomitting in
rats.
Thanks in advance,
John
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The following message was posted to: PharmPK
Hi
At 0.06 mg per day-7 days i think there is no visibles adverses
effects But data of chronic toxicology talk about modication of
conditioned reflexes at 1 mg/kg in rats.
Using TEA like drug solvant for injection contains risks and i will
be hard to expected transposition in humans
Had you try stability in glucose 5 % solution? had you try
lyophilisation formulation of you drug and and rapid dissolution in
glucose or serum salt before administration?
David, Hospital pharmacist, France
hope this helps
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