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The first point I would like to make here is that 5 mins is too late a
time point in animals. To the extent possible, 1 min time point should
The reason you see lower concentration at 5 mins than 15 mins is local
precipation at the site of injection in the vein (may be it is a good
idea to go for slow infusion).
This could be evaluated by following a simple technique. Dilute the
injection volume (actual volume dosed in rat) 10x, 20x and 50x in buffer
and blank rat plasma. Then centrifuge the samples to collect the
supernatant and analyze for the amount of drug. This could give us
reasonable information on drug solubility and propensity to precipitate
following IV injection.
Due to sink effect, the precipitated drug is solubilized in large
biological fluid volume and the impact is not seen beyond 15 mins.
The possible way to overcome this issue and get reasonable results is to
test the lowest possible IV dose, subject to the sensitivity of the
This phenomenon infact highlights the importance of studying the effect
of dilution on IV formulations.
Hope this helps and not too late!
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